FIFTH INTERNATIONAL CONGRESS ON CANCER, HELD IN PARIS, 16-22 JUL 50

• Document Type: CREST
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80-00926A002700030016-4
• Release Decision: RIPPUB
• Original Classification: C
• Document Page Count: 291
• Document Creation Date: December 15, 2016
• Document Release Date: September 11, 2003
• Sequence Number: 16
• Publication Date: November 8, 1950
• Content Type: REPORT

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V' CONGRES INTERNATIONAL v25X1
DU CANCER
25X1
PARIS 16-22 Juillet 1950
Sous le Haut Patronage de
M. Vincent AURIOL
Pr?dent de la Republique Francaise
Organise par l'UNION INTERNATIONALE CONTRE LE CANCER
sur !Invitation et avec to collaboration
de la Ligue Francaise contre le Cancer et de l'U. N. E. S. C. 0.
avec Nide financiere du C. C. l.C. M.S.
et place sous les auspices de l'O. M.S.
Siege du Congres
LA SORBONNE, 47, rue des Ecoles
PARIS
HERMANN & C'e, EDITEURS
6, Rue de la Sorbonne, 6
1950,
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ye CONGRES INTERNATIONAL
DU CANCER
PARIS ? 16-22 juillet 1950
Sous le Haut Patronage de
M. Vincent AURIOL
Pr?dent de la R6publique Frangaise
Organise par l'UNION INTERNATIONALE CONTRE LE CANCER
sur l'invitation et avec la collaboration
de la Ligue Francaise contre le Cancer et de l'U. N. E. S. C. 0.
avec Nide financiere du C. C. LC:M.S.
et place sous les auspices de l'a M.S.
Siege du Congres
LA SORBONNE, 47, rue des Ecoles
PARIS
HERMANN & Cle, EDITEURS
6, Rue de la Sorbonne, 6
1950
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ye CONGRtS INTERNATIONAL DU CANCER
PARES -- 16-22 JulIlet 1950
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CO MITE EXECUTIF
Pr?dent: M. le Docteur A. LACASSAGNE
Professeur au College de France
Directeur de la Section Biologique et Medicale
de l'Institut du Radium
Membre de l'Academie des Sciences
et de l'Academie Nationale de Medecine
M. Justin GODART, ancien Ministre
Membre de l'Academie Nationale de Medecine
President de l'Union Internationale contre le Cancer et Pr?dent
de la Ligue Franeaise contre le Cancer
Seeretaire General : M. le Professeur V. LE LORIER
Membre de l'Acadernie Nationale de Medecine
Secretaire General de la Ligue Francaise contre le Cancer
Secretaire General Adj. de l'Union Internationale contre le Cancer
Secretaire General Adjoint : M. le Docteur F. DENOIX
Directeur de la Section du Cancer
a l'Institut G.-Roussy, a Villejuif
Tresorier : M. Bernard H. FLURSCHEIM
Membre du Comite Executif
de l'Union Internationale contre le Cancer
Membre du Conseil d'Administration
de la Ligue Francaise contre le Cancer
Secreta ire Administrant : M. TROUE
Tresoriere Adj. de l'Union Internationale contre le Cancer
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PRESIDENT D'HONNEUR
M. le Docteur H. HARTMANN
Professeur honoraire a la Faculte de Medecine de Paris
Membre de l'Academie des Sciences
et de FAcadernie Nationale de Medecine
COMITE DU PROGRAMME
Pr?dent : M. le Docteur Ch.OBERLING,Professeur a la Faculte de Mede-
cine de Paris, Directeur de l'Institut Gustave-Roussy (section de la
recherche).
Membres : Professeur A. HADDOW (Grande-Bretagne).
Professeur W. WASSINK (Pays-Bas).
Professeur H. SCHINZ (Suisse).
Professeur A. CLAUDE (Belgique).
Professeur W. U. GARDNER (U. S. A.).
Professeur C. HUGGINS (U. S. A.).
Professeur D. BRACHETTO-BRIAN (Argentine).
Professeur P. RONDONI (Italie).
Professeur Y. HOCHMANN (Israel).
Professeur J. ENGELBRETH-HOLM (Danemark).
Professeur F. LUCASZCZYK (Pologne).
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COMITE D'ORGANISATION DU 'TRAVAIL
Premiere branche. ? Biologie et experimentation
Professeur Ch. OBERLING
Deuxi? branche. ? Pathologie, clinique et therapeutique
SFCTIONS. Appareil respiratoire : Docteur J. M. LEMOINE, Medecin de
l'Institut Gustave-Roussy.
Tube digestif : Docteur H. REDON, Chirurgien des Hopitaux
de Paris, Chirurgien de l'Institut Gustave-Roussy.
Appareil genito-urinaire : Docteur P. DELINOTTE, Chirur-
gien des Hopitaux de Paris.
?
Teguments et glande mammaire : Docteur J. COURTIAL, Me-
decin de la Fondation Curie.
Sguelette, sang : Professeur P. MOULONGUET, Directeur du
Centre des tumeurs a l'Hopital Tenon.
Troisieme branche, ? Lutte sociale
Docteur P. F. DENOIX, Chirurgien des Hopitaux de Paris
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COMTE D'HONNUR FEMININ
Presidents d'Honneur :
Madame Vincent AURIOL.
V ice-Presidentes :
Madame Gaston MONNERVILLE. Madame Pierre de GAULLE.
Madame Jacques FOURCADE. Madame Gustave ROUSSY.
Madame Georges BIDAULT. Madame Leon BINET.
Madame la Baronne GUILLAUME, Ambassade de Belgique a Paris.
Lady HARVEY, Ambassade de Grande-Bretagne a Paris.
Madame J. TORRES BODET.
Madame FISCHER, Ambassade d'Israig a Paris.
Princesse YUKANTHOR, Vice-Presidente de l'Union Francaise.
Madame de MORAES.
Madame Marie H?ne LEFAUCHEUX, Vice-Presidente de l'Union Fran -
caise.
Madame THOME PATENOTRE, Senateur.
Madame Felix EBOUE, Senateur.
Madame Maurice PETSCHE.
Madame PICHON LANDRY, President du Conseil National des Femmes.
Madame LE BRET, Presidente d'Honneur de la LIGUE FRANcAISE
contre le CANCER.
Madame VERLOME.
Madame LEONARD.
Madame KRAEMER BACH, Vice-Presidente du Comite
internationale.
Madame ABRAMI.
Princesse d'AREMBERG.
Madame V. AUGAGNEUR.
Madame
Madame
Madame
Madame
Madame
Madame
Madame
Madame
Madame
Madame
Madame
Madame
BARBIZET.
BARRAGUE.
BIZARDEL.
Pierre BLOCH.
BOREAU.
Claude BOURDET.
Yves BRAYER.
Jean CASSOU.
CHAINTRE.
Leon CIBIE.
CONTANT.
CORBIN.
Madame Aime COTTON.
Madame DAVID WE ILL.
Madame Maurice DUPLAY.
Madame Jean DUPUY.
Madame FRUH.
Madame FUNCK-BRENTANO.
de Legislation
3
Madame JUSTIN-GODART.
Madame GOETZE.
Madame HARTMANN.
Madame HEIMANN.
Madame HUGUENIN.
Madame HUISMAN.
Madame de HURTADO.
Madame INGRAND.
Madame KAHN SRIBER.
Docteur Simone LABORDE.
Madame LAZAREFF.
Madame Jacques LE BRET.
l3aronne LE LASSEUR.
Madame LELORIER.
Madame Charles LIEVRE.
Madame de L IPKOVSK I.
Duchesse de MAILLE.
Madame MALLET.
Madame MAXIME.
Madame Armand MAYER.
Madame Maurice MAYER.
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Docteur Genevieve MICHON.
Comtesse de PIEPAPE.
Princesse de POLIGNAC.
Madame RAMART-LUCAS.
Madame REDON.
Princesse de ROBECH.
Comtesse Cotic de ROCHEFORT.
Madame Jules ROMAINS.
Baronne Guy de ROTHSCHILD_
Madame SAINT-GIRONS.
Madame Maurice SCHUMANN.
Madame SMADJA BOUTBIEN.
Madame SMOL.
Madame Marguerite TROUE.
Madame UTRILLO.
Madame de VENDEUVRE.
COMTE DE PROPAGANDE
ET DE PUBLICITE
Mesdames A. HEIMANN, Presidente.
V. AUGAGNEUR.
Pierre BLOCH.
Claude BOURDET.
CHAINTRE.
LIEVRE.
MAXIME.
SMADJA BOUTBIEN.
Messieurs A. BLAKESLEE.
G. BOREAU
Docteur P. CIBRIE.
GAYMAN (radio).
Professeur L. JUSTIN-BESANCON.
Docteur I. LAVEDAN.
Professeur V. LE LORIER.
Professeur F. LEMAITRE.
Docteur F. LE SOURD
P. Mc GRADY.
G. MOLLAT DU JOURDIN.
H. MOUREU.
L. VIBOREL.
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UNION' INTERNATIONALE
CONTRE ,LE CANCER
(International Union against Cancer)
6, Avenue Marceau. Paris (89.
Agreee par l'OMS
(affiliated with W. H. 0.)
Membre fondateur du C. C. I. C. M. S.
Telephone: Banque: SOCIETE GENERALE Cheques Postaux
ELYsees 10, Place Victor,Hugo, Paris xvie PARIS
92-80 Compte 13.390 4437
COMITE EXkCUTIF (EXECUTIVE COMMITTEE)
iBureau.? Pr?dent: M. Justin GODART (France).
Vice-Presidents regionaux :
Professeur E. V. COWDRY (Etats-Unis) ;
Professeur A. PRUDENTE (Amerique latine) ;
Lord AMULREE (Empire Britdnnique) ;
Professeur V. KHANOLKAR (Asie) ;
Professeur E. BERVEN (Europe):
Secretaire General : Professeur J. M'AISIN (Belgique).
President du Ve Congres du Cancer : Professeur A. LACAS,-
SAGNE (France). a
President du Comae Executif de l' 1. C. R. C. : Professeur I.
MILLAN, es-qualite (Mexique).
.Pr?dent du Comite Financier :M. Boris PREGEL.
Secretaire General-adjoint : Professeur V. LE LORIER (France).
Tresorier : M. B. H. FLURSCHEIM (Etats-Unis).
iMembi^es (Members) : Professeur M. ASHOUR (Egypte) ; Professeur X.
CHAHOVITCH (Yougoslavie) ; Professeur A. HADDOW (Grande-
Bretagne); Professeur LHERMITTE (Saint-Siege); Professeur E. MI-
NOPOULOS (Grece) ; Pr. R. POSADA (El-Salvador) ; Professeur E.
BIANCHI (Suisse); Professeur A. RAHAUSEN (Chili); Professeur A.
RODRIGUEZ (Portugal) ; Professeur R. WILLIS (Australie).
Tresorier-adjoint et Secretaire administrant Mlle M. MOUE.
Membre d'Honneur (Honorary Members) : M. le Docteur BROCK CHIS-
HOLM, Directeur general de l'O. M. S. (W. H. 0.) ; Madame le Doc-
teur I. ZHUKOVA, Conseiller hi l'U. N. E. S. C. 0.
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CONSEIL SCIENTIFIQUE DE L'U. I. C. C.
(International Cancer Research Commission).
Comite Executif (Executive Committee)
President Professeur I. MILLAN (Mexique).
Suppleant : Alternate: Professeur E. LEBORGNE (Uruguay).
Membres (Members) : Professeur E. V. COWDRY (Etats-Unis) ; Pro-
fesseur V. R. KHANOLKAR (Inde) ; Professeur J. MAISIN (Belgique)
Professeur A. HADDOW (Grande-Bretagne).
Membres supnleants : Alternates : Professeur W. U. GARDNER (Etats-
Unis) ; Professeur TU-SHAN YUNG (Chine) ; Professeur A. LACASSA-
GNE (France) ; Professeur J. ENGELBRETH-HOLM (Danemark).
MEMBRES DU CONSEIL SCIENTIFIQUE
DE L'UNION
(International Cancer Research Commission)
ARABIE SAOUDITE Dr. R. PHARAMON, Ministre de l'Ara-
bie, a Paris.
ARGENTINE Pr. Juan Esteban PESSANO, Sec. Salud
Publica de la Naccion, D. de Neopla-
sias Pozos 2073, Buenos-Aires.
AU STRALIE Dr. Douglas PEARCE 12, Collins Street,
Melbourne.
AU T RICHE Dr. J. KRETZ, Brahlmsplatz, 5, Vienne
IV.
BELGIQUE Pr. J. MAISIN 61 Voer des Capucins,
Univ. de Louvain.
BOLI V IE Dr. Fernandez FERRUFINO Hnos,
Machego no 908, La Paz.
BRE S IL Pr. A. PRUDENTE, Sdo Paulo.
BUL GARIE Dr. PAPASOV, rue Strandja 136, So-
fia (2).
CAN ADA (L'ancien membre, le Pr. RICHARDS est
(Made, pas de remplaeant en atten-
dant).
CHILI Pr. Alberto RAHAUSEN Int. Nat. del
Radium A. Zanartu 1000, Santiago.
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CHINE Dr. TU SHAN JUNG, dept. of Radio-
logy, Pekin Union Medical Colle
Pekin.
COLOMBIE Dr. Ruben A. GARCIA, Institut du Ra-
dium, Bogota.
CUBA Pr. N. PUENTE DUANY K. 503, Veda-
do, Habana.
DANEMARK Pr. ENGELBRETH-HOLM, Univ. Pat..
Anatomie Inst. Frederik Vej
Cop enh ague.
DUCHE LUXEMBOURG Er. S. NERTZ, 7, Grande-Rue et rue de
Fosse, Luxembourg.
EGYPTE Pr. M. A. ASHOUR, Section Path.
Ministere de la Sante Publique,
Caire.
EL SALVADOR Don Ricardo POSADA, Universidad de
El Salvador. San Salvador.
FINLANDE Dr. Osmo JARVI, Universite de Turku
Kristinemk I, Turku.
FRANCE Pr. A. LACASSAGNE, Lre de Biologie,.
Inst. du Radium de l'Universite de
Paris, 26, rue d'Ulm, Paris.
GRANDE-BRETAGNE Pr. A. HADDOW, Chester Beatty-Re-
search Inst. Royal Cancer Hospital,,
Fulham Road, London SW 3.
GRECE Dr. E. M. MINOPOULOS,33, ay. Fran-
klin-Roosewelt, Avon Fontainebleau
1 (France).
ISLAIVDE Pr. Niels DUNGAL, Dep. of Pathology,
Univ. of Reykjavik, Sudurgat 12,,
Reykjavik.
INDE Pr. V. K. KHANOLKAR Direct. of La.
Tata Memorial Hospital, Bombay.
HONDURAS S. Excellence, Don Antonio VIDAL,
Ambassadeur Honduras, Paris.
INDOCHINE M. S. LONG, Institut du Cancer, rue
Richaud, Hanoi.
IRAN Dr. A. A. RADJI, Bankemelli Hospital:
Teheran.
IRAK Pr. Salman FAIK, As. Prof. Royal Col-
lege of Medecine, Bagdad.
ISRAEL Dr. A. HOCHMANN, Radium and Tu-
mor Inst. Hadassah Hosp. ,Jerusalem.
ITALIE Pr. E. PENTIMALLI, 1st. de 'Patologia
Gle, S. Andrea Dame 8, Naples.
JAPOIV Pr. KINOSHITA, Osaka Univ. Osaka._
KOREE Pr. II SUN YUN, Dept. of Pathology,.
Seoul Univer. Medical School Seoul.
LIBAN Dr. J. ZAHAR 36, ay. d'Italie, Paris.
MEXIQUE Pr. I. MILLAN, Director of tumor Cli-
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nics Gal Hosp. avenida Vera Cruz 69,
Mexico D. F.
NOUVELLE-ZELANDE Sir James ELLIOT, 43, Kent Terrace,
Wellington.
NICARAGUA Dr. Fernando VELEZ PAIZ, Managua
D. N.
NOR VE GE Pr. Leiv KREYBERG, Dept of Patholo-
gy Univ. of Oslo.
PANAMA (Rep. de) Dr. Ernest ZUBIOTA, P. Box, Panama.
PAYS-BAS Pr. KORTEWEG, Lab. Antoni Van
Leeuwenhoek - huis Sarphatistraat,
108, Amsterdam.
PERDU Dr. Eduard CACERES, Lima:
PHILIPPINES Dr. Juan A. ARCELLANA, College of.
Med. & Philippine Gal Hosp. Univ.
of Philippines, ManiIle.
POLO GNE Pr. F. LUKASZCYK, Directeur de l'Inst.
du Radium, 15, rue Wawel-ska,
Varsovie.
PORTUGAL Lima BASTO, 21 ay. Deensores Chaves,
Lisbonne.
SIAM Dr. Chanai RUANGSIRI, Chulankarana
Univ. Bangkok.
SUEDE Pr. Elis BERVEN, Clinical Director of
the Radiumhemmet Caroline Hospi-
tal, Stockholm.
SUISSE Pr. H. R. SCHINZ, Roentgen Inst. &
Radiotherap. Klinic Kantonspital,
Zurich.
TqatcosLoVAQUIE Pr. H. SIKL, Dpt of Pathology, Univ.
Charles IV, Prague.
THAILAND Dr. L. BINBAKYA, Bangkok.
TU NIS IE Pr. ANDERSON, Dr du Laboratoire de
Cancerologie de l'Inst. des Hautes-
Etudes, Tunis.
TURQUIE Dr. M. CINCIN, Ankara.
UNION SUD-AFRICAINE Lt-Col Maurice WEINBREN, X-ray dept
Chamber of Mines Hospital, P. 0.
Box 774, Johannesburg.
URUGUAY Pr. Felix LEBORGNE, Ibucuy 1210,
Montevideo.
U. S. A. Pr. E. V. COWDRY, Washington Univ.
Med. School, Saint-Louis (M. 0).
VENEZUELA Dr. Hermogenes RIVERO, Inst. de
Oncologia Luis Rasetti, Caracas.
YO U GOSLAVIE Pr. X. CHAHOVITCH, Depart. de Pa-
thologie, Univ. de Belgrade, 16, Bd
de l'Armee Yougoslave, Belgrade.
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LIGUE FRANgAISE CONTRE LE CANCER,
6, avenue Marceau, Paris (8e).
Reconnue d'utilite publique. Cheque postal 561.13 Paris.
Decret du 22 nov. 1920. 'releph. Elysee 92-80.
Sous le Haut Patronage de Monseigneur FELTIN
et de Madame Vincent AURIOL.
I. ? CONSEIL D'ADMINISTRATION
Pr?dent :
M. Justin GODART, ancien Ministre, membre de l'Academie Nationale de
Medecine.
Vice-Pr?dent :
Professeur H. HARTMANN, membre de l'Institut et de l'Academie Natio-
nale de Medecine.
Secretaire general : Professeur V. LE LORIER, membre de l'Academie
Nationale de Medecine.
Secretaire general honoraire : M. R. LE BRET (1- in memoriam).
Secretaire general adjoint : Professeur BASSET, tmembre de l'Academie
Nationale de Medecine.
Seeretaire adjoint honoraire : Docteur Sonia FABRE (+ in memoriam).
Tresorier : M. PATRY.
Membres :
Professeur BASSET; Docteur S. BLONDIN ; Cl. CHAVANE, notaitt ;
Docteur DENOIX ?H. B. FLURSCHEIM ; Professeur R. HUGUENIN;
Professeur A. LACASSAGNE ; Madame Armand MAYER; Professeur
R MOULONGUET ; Docteur A. TAILHEFER.
Conseils juridiques : Messieurs DURNERIN,avocat au Conseil d'Etat et a la
Cour de cassation ; BOCCON-GIBOD, avoue ; JOBIT, avocat a la Cour.
Secretaire administrative : Docteur Genevieve MICHON.
Conseiller technique a la Propagande : Lucien VIBOREL.
II. ? COMITE SCIENTIFIQUE
BERARD, Professeur honoraire de Clinique chirurgicale a la Faculte de
Modecine de Lyon. Membre de l'Academie Nationale de Medecine. ?
BRUMPT, Professeur de parasitologie a la Faculte de Medecine de Paris,
Membrade l'Academie Nationale de Medecine.
DRIESSENS, Professeur a la Faculte de Medecine, Directeur du Centre
anticancereux ,de Lille.
HARTMANN, ,Professeur honoraire a la Faculte de Medecine de Paris,
Membre de l'Institut. '
HUGUENIN, Professeur a la Faculte de Medecine de Paris, Directeur de
l'Institut Gustave-Roussy.
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LACASSAGNE, Professeur au College de France, Directeur de la Section,
biologique et medicale de l'Institut du Radium.
LAMARQUE, Professeur a la Faculte de Medecine du Centre anticance?
reux de Montpellier.
MAISIN, Professeur a l'Universite de Louvain.
MOULONGUET, Professeur a la Faculte de Medecine de Paris.
NICOD, Professeur a l'Universite de Lausanne.
OBERLING, Professeur a la Faculte de Medecine, Directeur de l'Institut
des Recherches sur le Cancer Gustave-Roussy.
III. ? COMITk CENTRAL D'ASSISTANCE
ET DE PROPAGANDE
Presiderite : Madame Armand MAYER.
V ice-Presidente : Madame Jacques CONTANT..
Tresorieres : Madame Adrien DUTEY-HARISpE, Madame Jacques LE
BRET.
Secretaire du Comite Docteur Genevieve MICHON.
Presidente d'honneur : Madame LE BRET.
Vice-Presidentes d'honneur : Princesse Ernest d'ARENBERG, Madame GER?
NEZ.
Presidente d'honneur de la Section d'Assistance : Madame Henri HART-
MANN.
Comite d'honneur :
Madame Louis BAZY. Madame Maurice GRIMPREL.
Md'dame CORBIN. Duchesse della ROCHEFOUCAULD.
Madame la Generale BUAT. Madame la Generale LYAUTEY.
Duchesse de DURAS. Madame Georges MENIER.
Comtesse G. de CHAVAGNAC. Madame R. PATENOTRE.
MAame ENOS. Madame Eugene SCHNEIDER.
Madame P. FUNCK-BRENTANO. Madame SOMMIER.
Madame ENOS. Madame Eugene SCHNEIDER.
Madame Justin GODART. Madame VIELLARD.
Comtesse de GRAMONT. Madame Fr. de WENDEL.
Comite d'assistance et de propagande :
Madame ARNAUD.
Madame BERTEVILLE.
Madame G. BILLEY.
Madame BOIVIN.
Madame COMBES.
Madame DUPLAY.
Madame EYROLLES.
Madame GAY.
Madame RUDE.
Mademoiselle LECLERC.
Madame LEDRU.
Madame MAIRE.
Madame MALLET.
Madame Paul MAYER.
Mademoiselle de MONBELL IARD.
Madame MORIN.
Madame NORBERT-NORD.
Mademoiselle PROUST.
Madame ROGER.
Commandant SALES.
Madame SCHAER-VEZINET.
Madame SELLIER.
Madame TROULLIER.
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LEGENDE DU PLAN I
1. Grand amphitheatre (s?ce inaugurale et colloques).
2. A. Amphitheatre Richelieu (communications de Biologie le matin).
4. C. Amphitheatre Guizot (communications de Biologie le matin et de
Pathologie l'apres-midi).
5. D. Salle L. Liard (communications de Biologie le matin et de Pathologie
l'apres-midi).
6. E. Amphitheatre Turgot (communications de Biologie le matin et de
Pathologic l'apres-midi).
7. G. Amphitheatre Quinet (Projections cinematographiques).
8. H. Amphitheatre Michelet (communications de Lutte Sociale l'apres-
midi).
13-14. Salle de correspondance.
15. Bar.
18. Lavabo.
20. Entr? du Congres (rue des Ecoles).
25. Hall d'entree (Secretariat, contrale des inscriptions au Congres, bureau
du tourisme et d'accueil feminin).
26. Bureau de poste.
27. Bureau de Change.
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4
La. Sorbonne.
A
Metro Luxerri4oully
2,
L'Eeolecle. MOS ocine
33
Metro Od-P.07?-
3
La. Facutte de Me decine
c
Metro 5a1rd-Michel
4
Le Cota.ge de. rednce
D
Metro Mo-ubert-Mutuatite"
5
L'Jnstitat cLo Raolichrn-
E
Panthion.
6
L'Hapitat Grbriq..
F
Notve-Da_ma
7
L'Ecole de Physhre e,t
de Chirn
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?COUR
I HON NEUR
,
GALERiE 11 ROBERT
.6FIAND
AMPHITHEATRE
2.6 1 27
25
-J
cies
Plan no 1
Ecgle.s'
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RENSEIGNEMENTS GENERAUX
Siege du Congres : la Sorbonne
Toutes les seances du Congres se tiendront dans les amphitheatres de la
Sorbonne (voir Plan I : Grand Amphitheatre = no 1 ; Richelieu = no 2 A ;
Guizot = 4 C; Liard = 5 D; Turgot = 6 E; Michelet = 8 H).
Les entrees du Congres se trouvent au 47 de la rue des Ecoles (n? 20 du
Plan I).
Moyens de communications
Metropolitain : lignes 4 et 10, station Odeon. Ligne de Sceaux (Cite Uni-
versitaire), station Luxembourg (voir Plan II).
Auto bus : lignes 27, 38, 63, 77, 84, 85, 86. Consulter le plan special contenu
dans la pochette individuelle.
Secretariat
Le secretariat du Congres siege dans le hall d'entree de la Sorbonne (no 25
du Plan I). Il sera ouvert des le dimanche matin 16 juillet, immediatemen t
apres la terminaison de la s?ce inaugurale. Ii restera ouvert ce jour-l?
jusqu'a 19 heures. Les jours suivants, il fonctionnera en permanence de
9 heures A 17 heures.
Les congressistes sont pries de retirer personnellement, au Secretariat,
det le dimanche 16 juillet, la pochette individuelle preparee a leur nom.
us voudront bien egalement, des leur arrivee : 10 s'inscrire (s'ils desirent
y prendre part) au banquet par souscription, qui aura lieu le jeudi soir,
20 juillet, a l'Hotel George V, avenue George-V, 8? arrondissement. Le prix
de la souscription est de 2.000 francs; 20 s'adresser au bureau du tourisme
(hall d'entree, no 25 du Plan I) pour tous renseignements concernant les
speaacles, excursions, voyages, etc...
Membres associes
Les membres associes du Congres trouveront une enveloppe A leur nom
dans la pochette du membre titulaire qui les accompagne. Ils recevront
ainsi le programme special des receptions, promenades et visites organisees
pour eux.
Pour tous les renseignements concernant les membres associes, priere de
s'adresser au Secretariat.
Logement
Pour toutes les questions relatives au logement, priere de s'adresser au
bureau du tourisme.
Postes. Telegraphe. Telephone
Un bureau de Postes, ala disposition des congressistes est installe dans le
local correspondant au no 26 du Plan I.
En outre, les congressistes trouveront des cabines telephoniques an
leo etage, en haut du grand escalier, montee cote gauche.
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Passeports
Le bureau du tourisme pourra, a la demande des congressistes, s'occuper
des questions de passeports et de visas.
Banque
Un bureau de change est installe dans le hail d'entree (no 27 du Plan I).
Salons de 'conversation et 'de airrespondance
Des salons pour la conversation sprit A la disposition des congressistes au
1., &age. -
Unel salle est amenagee pour la lecture ,et la' correspendance (no. 13 et 14
du Plan I).
Bar
?
Les congressistes trouveront des rafraicliissements dans le local corres-
pondant au no 15 du Plan I.
Dejeuner
Voir la liste des restaurants proches de la Sorbonne, avec leur adresse et
leurs prix.
Informations
Pendant toute la duree du Congres, les renseignements susceptibles d'in-
teresser les congressistes seront inscrits sur un tableau reserve A cet usage,
dans le hall d'entree. ' ? '
En outre, des informateurs benevoles porteurs d'un brassard, seront A la
disposition des congressistes, pour leur fournir des renseignements comple-
mentaires (brassard rouge = informateur de langue anglaise; brassard
bleu = de langue allemande ; brassard vert = de langue espagnole).
Exposition
Une exposition contenant des documents sin' differents aspects scienti-
fiques, cliniques et statistiques du cancer occupe des salles du 1., etage.
Dans les memes locaux sont presentes divers livres et publications relatifs
au cancer. 0, .
Cinquantenaire de la decouverte du radium
En meme temps que le V. Congres international du Cancer, on celebrera
le cinquantenaire de la decouverte du radium, dans les beaux de rEcole
superieure de Physique et de Chimie industrielles de la Ville de Paris, 10, rue
Vauquelin (voir Plan II, no 7), on Pierre et Marie Curie firent leur decouverte.
Une notice speciale sur les reunions et ceremonies du cinquantenaire
(auxquelles les membres du Congres ,du. Cancer seront admis) est incluse
dans la pochette individuelle.
Cours sur le cancer
?
Une subvention du. C. C. I. C. M. C. a peinns d'organiser a la Faculte de
Medecine de Paris, un cours special a l'intention des medecins et etudiants,
portant sur differents sujets de cancerologie, qui seront traites par des spe-
cialistes etrangers venus a l'occasion du Congres.
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PROGRAMME SCIENTIFIQUE .DU CONGRES
I. ? COLLOQUES
Tous les CoRogues se tiendront dans le Grand Amphitheatre (no 1 du
plan I), le matin a partir de, 9 heures pour ceux de Biologie et de Lutte
sociale, l'apres-midi a partir de 14 heures pour ceux de Pathologic, Clinique
et Therapeutique.
A chacun de ces colloques, trois conferenciers commenCeront par exposer,
en 20 minutes chacun, leur conception personnelle du sujet. (Un r?m?e
ces conferences sera distribue aux congressistes presents).
Apres quoi, le President conduira la discussion 'et les echanges de vues
entre les conferenciers et les argumentateurs invites a l'avance a y prendre
part.
A la fin de cette discussion, le President pourra dormer la,parole 4, des, cap;
gressistes de l'assistance.
HORAIRES, TITRES ET PARTICIPANTS DES COLLOQUES
Le lundi 17 juillet a 9 h.
Les constituants morphologiques et biochimiques des cellules cancereuses :
Pr?dent: M. E. V. GOWDRY (Saint-Louis).
Conferenciers : MM. A. V. ALBERTINI (Zurich), A. BUTENANDT
(Tubingen), Ch. OBERLING (Paris).
Argumentateurs : MM. C. BARIGOZZI (Milan), H. V. EULER (Stoc-
kholm), R. GARRIGUES (Lyon), A. I. LANSING (Saint-Louis),
P. LEBLOND (Montreal), G. MOBERGER (Stockholm).
Le mardi 18 juillet a 9 h.
Mode d'action des agents cancerigenes sur les cellules :
Pr?dent: Mme G. M. BONSER (Leeds). -
Conlerenciers : MM. A. HADDOW (Londres), R. LATARJET (Paris),
J. MAISIN (Louvain).
Argumentateurs : MM. I. BERENBLUM (Israel), J. ENGELBRETH-
HOLM (Copenhague), A. LIPSCHUTZ (Santiago du Chili), P. PEA-
COCK (Glasgow), H. P. RUSH (Madison), A. TANNENBAUM
(Chicago).
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1
Le rnercredi 19 juillet A 9 h.
Nature et role des virus dans le cancer:
Pr?dent: M. J. J. BITTNER (Minneapolis).
Conferenciers : MM. A. CLAUDE (Bruxelles), F. DURAN-REYNALS
(New-Haven), R. D. PASSEY (Leeds).
Argumentateurs : MM. W. T. ASTBURY (Leeds), W. R. BRYAN
(Bethesda), J. G. CARR (Londres), R. G. GOTTSCHALK (Dal-
las), M. GUERIN (Paris), D. H. MOORE (New-York).
Le jeudi 20 juillet a 9 h.
Bases experimentales de to chimiotherapie du cancer :
Pr?dent: M. E. C. DODDS (Londres),.
Conferenciers : MM. P. DUSTIN (Bruxelles), Ch. HUGGINS (Chicago),
M. J. SHEAR (Bethesda).
Argumentateurs : MM. E. BOYLAND (Londres), N. P. BUU-HOI
(Paris), K. DOBRINER (New-York), P. C. KOLLER (Londres),
' H. LETTRE (Heidelberg), C. C. STOCK (New-York).
Le vendredi 21 juillet A 9 h.
Eta blissement et interpretation des statistigues en cancerologie :
Pr?dent: M. W. F. WASSINCK (Amsterdam).
Conferenciers : MM. J. CLEMMESEN (Copenhague), G. DENOIX
(Paris), Mlle M. MACDONALD (New-York).
Argumentateurs : MM. H. F. DORN (BetheSda), Mlle El. MACDONALD
' (Houston), J. M. MAY (New-York), H. SCHINZ (Zurich), Mlle S.
SIMON (Bruxelles), J. J. VERSLUYS (Hillegom).
Le lundi 17 juillet a 14 h.?
Definition et traitement des melanomes matins de la peau :
President : M. G. MIESCHER (Zurich).
Conferenciers : MM. M. GORDON (New-York), M. POLAK (Buenos-
Aires), A. PRUDENTE (Sao Paulo).
Argumentateurs :MM. T. R. MILLER (New-York), R. RAVEN (Londres),
C. SAYAGO (Santiago du Chili), B. SYLVEN (Stockholm),
V. VILTER (Paris).
La, rnardi 19 juillet A 14 h.
Interretation; classification et traitement des turneurs des glandes salivaires :
Pr?dent: M. J. ROUX-BERGER (Paris).
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Conferenciers : MM. H. AHLBOM (Stockholm), G. GRICOUROFF
(Faris), H. MARTIN (New-York).
Argumentateurs : MM. P. COGNIAUX (Bruxelles), H. HAMPERL
(Marbourg), L. KREYBERG (Oslo), V. PRICOLO (Milan), H. RE-
DON (Paris), S. H. WARREN (Boston).
Le mercredi 19 juillet a 14 h.
Classification, interpretation et diagnostic des tumeurs du testicule :
Pr?dent: M. R. A. MOORE (Saint-Louis).
Conferenciers : MM. F. J. DIXON (Saint-Louis), P. MASSON (Mon-
tr?), G. TEILUM (Copenhague).
Argumentateurs: MM. W. W. GREULICH (Stanford), H. HINGLAIS
(Paris), M. MELLA VELOSO (Santiago du Chili), F. K. MOSTOFI
(Washington), J. NIELSEN (Copenhague), N. PENDE (Rome),
A. SYMEONIDIS (Bethesda).
Le jeudi 20 juillet a 14 h.
Essai de classification des tumeurs bronchiques et tears indications thera-
peutiques particulieres :
Pr?dent: M. P. A. BARCIA (Montevideo).
a Conferenciers : MM. A. BERGSTRAND (Stockholm), R. HUGUENIN
(Paris), W. L. WATSON (New-York).
Argumentateurs : MM. F. BIGNAMI (Rome), C. L. JACKSON (Balti-
more), P. DESAIVE (Liege), Mme G. HILTON (Londres), N. MON-
TANINI (Rome), P. SANTY (Lyon), M. A. SIMON (Montreal).
Le vendredi 21 juillet a 14 h.
Nomenclature et essai de classification histologique des tumeurs du sque-
lette d'origine reliculo-endotheliale.
Pr?dent: M. D. BRACHETTO-BRIAN (Buenos-Aires).
Conferenciers : MM. R. LEROUX (Paris), A. H. T. ROBB-SMITH
(Oxford), I. SNAPPER (New-York).
Argumentateurs: MM. P. BJERRE-HANSEN (Aarhus), H. DRIEUX
(Paris), V. R. KHANOLKAR (Bombay), PICARD (Louvain),
H. A. SISSONS (Londres).
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II. ? SECTION CINkMATOGRAPHIQUE
. . ,
Un amphitheatre special (Quinet, no 7 G du plan I) est affecte a la presen-
tation des films adresses par des congressistes.
Chaque film sera presente plusieurs fois au cours des seances permanentes
qui auront lieu tous les jours pendant la duree du Congres.
L'horaire des representations sera affiche iregulierement a la porte de
ramphitheatre.
LISTE DES FILMS REDUS.
1
I. CANCER : Le problethe 'obi diagnostic precoce: ? .Film sonore, 16 mm,
en couleur. Duree 30 minutes. Produit conjointement"par le Na-
tional Cancer Institute et l'American Cancer Society (U. S. A.)
Ce film traite du probleme du Cancer en general.
II. CANCER DU SEIN : Le probleme du diagnostic precoce. ? Film sonore,
16 mm, en couleur. Duree 34 minutes. Produit conjointement par
le National Cancer Institute et l'American Cancer Society (U.S.A.).
CANCFR GASTRO-INTESTINAL Le ,probleme du diagnostic pre-
coce. ? Film sonore, 16 mm, en coulenr. Diiree 30 minutes emit-
ron. Produit conjOintemerif par le National Cancer Institute et
l'American?Cancer Society (U. S. A.). ?
IV. LA SCIENCE CONTRE LE CANCER. ? Film sonore 16 mm, noir et
blanc. Duree 35 minutes environ. Ce film documentaire a ete
produit par le Department of Health and Welfare of the Canadian
Government, et le National Cancer Institute' (U.' S: A:)" 11 est
destine au public. Le texte explicatif de cc film est dit, pour la
version francaise, par Claude DAUPHIN.
V. EXAMEN .DES SEINS. ? Film instructif a l'intention d'un public
feminin. Film?sonore, 16 mm, en couleur. Duree 12 minutes. Pro-
duit conjointement par le National Cancer Institute et l'American
Cancer Society (U. S. A.).
VI. LA GASTRECTOMIE TOTALE. ? Ce film execute dans la Clinique
Chirurgicale de Bologne, illustre dans la premiere partie la tech-
nique de la gastrectomie totale de l'estomac, en cas de carcinome
diffus. Dans la seconde partie, des reproductions de radiographies
avant et apres l'intervention et une breve presentation des pieces
operatoires, choisies parmi les plus significatives se proposent de
demontrer les possibilites et les resultats de l'intervention radicale.
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Film 16 mm. Produit par le Professeur G. Gherardo FORNI,
Directeur de la Clinique Chirurgicale de Bologne (Italie).
VII. METHODES D'ETUDE IN VITRO DE LA REACTION DES CEL-
LULES AUX RAYONS X ET A D'AUTRES AGENTS. ? Film
muet, 16 mm, en couleur, Demontre les methodes d'etude des cel-
lules saines et malignes, sur cellules non colorees. Ii montre aussi,
fi l'aide de la microphotographie, les. modifications[ des cellules
apres traiteinent par rayons X. Produit par Robert SCHREK
M. D. Tumor Research Unit. Veterans Administration Hospital,
Hines, Illinois (U. A).
DrekpNgsTiq DIJ CANCER DE L'UTERUS PAR LES CELLULES
" EXVOLIEES. Film muet, 16 mm, en couleur. Duree 23 minutes
Realise par H. E,, NIE13URGS et E. R. PUND, Medical College of
Georgia a,Augusta.(U. S. A.). Il illustre les modifications produites
au Myeau du col ,uterin sous l'influence des hormones, ainsi que les
differents aspects cytologiques des differents types de cancers.
,
IX. DIVISION CELLULAIRE ET POISONS DE LA MITOSE. ? Film
sonore (en anglais et. en frangais). Duree 12 a 15 minutes. A ete
realise afin, de montrer Faction in vitro, et a l'aide du microscope
.a contraste de phases, de certains poisons de la division cellulaire.
Produit ,par le Pr. Hans LETTRE de l'Universite d'Heidelberg
(Allemagne).
X, DIAGNOSTIC PRATIQUE DU CANCER DU RECTUM. ? Film so-
nore, en francais, en 35 mm, en noir. Duree;dix minutes. F,tealise par
le Pr. MOULONGUET de la Faculte de Medecine de Paris,'avec
l'aide de la Ligue francaise contre le cancer.
XI. DIAGNOSTIC PRATIQUE DU CANCER DU SEIN.? Film sonore
en francais, en 35 mm, en noir, photographie et dessins animes.
Realise par les memes.
XII. LA LARYNGECTOMIE TOTALE. ? Film muet, 16 mm, en noir.
Texte en francais et en anglais. Duree 20 a 25 minutes. Produit
par le Dr J. LEROUX-ROBERT, oto-rhino-laryngologiste des
Hopitaux de Paris et de la Fondation Curie.
L'apres-midi du vendredi sera reserve a une discussion qui aura lieu 6
l'Amphitheatre Quinet, sur la valeur educative des films:dans la lutte contre
le cancer.
Note. ? Un certain nombre d'autres films non-sonorises seront presentes
dans les amphitheatres des sections, en meme temps que la communica-
tion de leur auteur.
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III. ? COMMUNICATIONS
La duree de l'expose a ete fixee a 10 minutes ; celle de la discussion de
,chaque communication a 10 minutes egalernent. Si la duree de l'expose
.depasse le temps prescrit, celle de la discussion sera diminuee d'autant.
L'horaire de chaque s?ce devant etre strictement respecte,la discussion
sera necessairement interrompue a l'heure prevue pour le debut de la com-
munication suivante.
Tous les amphitheatres sont equipes de facor a permettre des projections
Les orateurs sont pries de s'entendre, au debut de la seance dans laquelle
leur communication est inscrite, avec l'operateur charge des projections.
Priere d'informer prealablement le Secretariat en cas de film non-sonorise,
.devant etre projete au cours d'une communication, afln que l'appareil appro-
prie soit installe dans l'amphitheatre.
Les orateurs sont pries de remettre au Secretaire de in seance, des la fin
de leur expose, le texte de leur communication, dactylographie en 'double
exemplaire, pour qu'il puisse etre imprime dans les Comptes rendus du
Congres, qui seront publies dans les a Acta ?.
Les langues admises pour la presentation des communications sont :
l'allemand, l'anglais, l'espagnol, le frangais et le russe.
On trouvera aux pages suivantes deux tableaux synoptiques, indiquant
les seances et les amphitheatres on siegeront les differentes sections. Le
groupement des communications correspond -- autant qu'il a ete possible
-de le realiser ? au titre general de la section. Cependant, cot arrangement
n'a pas toujours Pu etre respecte, parce que la communication traite un
sujet special, on qu'elle est parvenue trop tard au secretariat.
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0
CD
0
0
0
0
0
CA)
0
0
TABLEAU SYNOPTIQUE DES SEANCES DE COMMUNICATION DE L'APRES-MIDI
BRANCHE : PATHOLOGIE ET LUTTE SOCIALE
Amphitheatre
Lundi 17
Mardi 18
Mercredi 19
Jeudi 20
Vendredi 21
4 C (Guizot)
Organes genito-uri-
naires males
(voir p. 137)
Cancers cutanes
(voir p. 143)
Cancers cutanes
(voir p. 148)
--,_,
Pathologie generale
(voir p. 153)
Communications di-
verses
(voir p. 159)
5 D (L. Liard)
Voies respiratoires
Voles digestives
Os et systeme san-
Chimiotherapie
Systeme nerveux et
(voir p. 165)
(voir p. 172)
guin
(voir p. 183)
corps thyrolde
(voir p. 177)
(voir p. 189).
6 E (Turgot)
Glandes salivaires et
Cancers de la ma-
Cancers uterins
Cancers uterins
Radiotherapie
mamelle
melle
(voir p. 207)
(voir p. 213)
(voir p. 218)
(voir p. 195)
(voir p. 201)-----
.
8 H (Michelet)
Lutte sociale
Lutte socialeLutte
sociale
Lutte sociale
Lutte sociale
(voir p. 225)
(voir'p. 231) ' :
' (Voir p: 237) '' '
(voir p. 243)
(voir p. 248)
: . . ?
,
0
CD
0
0
0
0
0
C.4
0
0
TABLEAU SYNOPTIQUE DES SEANCES DE COMMUNICATION DU MATIN
BRANCHE : BIOLOGIE ET EXPtRIMENTATION
Amphitheatre
tui 17
Mardi 18
Mercredi 19
Jeudi 20
Vendredi 21? ---
2 A(Richelieu)
Cancers et hormones
Cancers et hormones
Cancers provoques
Cancers provoques
Cancers provoques
4 C (Guizot)
(voir p. 29)
Cancers et virus
(voir p. 35)
Cancers et virus
(voir p. 40)
Microorganismes et
(voir p. 46)
Cytologie, Histolo-
(voir p. 52) ,
Cytologic. Hist olo -
(voir p. 58)
(voir p. 63)
cancers
gie
gie
(voir p. 68)
(voir p. 73)
(voir p. 78)
5 D (L. Liaid)
Chimiotherapie
Chimiotherapie
Chimiotherapie
Biochimie
Biochimie
experimentale
experimentale
experimentale
(voir p. 99)
(voir p. 105)
(voir p. 83)
(voir p. 89)
(voir p. 94)
6 E (Turgot)
Cancers transplantes
Biologie generale
Nutrition
Radiobiologie
Radiobiologie
(voir p. 109)
(voir p. 114)
(voir p. 120)
(voir p. 125)
(voir p. 130)
8 H (Miclielet)?
Communications
diverses
Protection contre les
agents cancerigenes
Communications
diverses
(voir p. 253)
(voir p. 257)
(voir p. 258)
Qr?
0
0
a xi
0
0
0
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PREMIERE BRANCHE
`BIOLOGIE ET EXPERIMENTATION
AMPHITHEATRE ? 2 A ? (RICHELIEU)
Lundi matin 17 juillet 1950 (de 9 h. A 12 h.)
SECTION: CANCERS ET HORMONES
Presidents.: H. M. EVANS et G. W. WOOLLEY
9 h. D - 9 b. 20 DRUCKREY H.? Constitution chimique et action des
substances cestrogenes et cancerigenes.
9 h. 20 - 9 h. 40 SYMEONIDIS A.? Studies on the induction of tumors
by a combination of carcinogenic agents and hormo-
nal effects.
9 h. 40 - 10 h. D MULBOCK 0. ? Influence of environments on the
mammary-tumor incidence in mice.
10 h. D - 10 h. 20 ? MEERSSEMAN F. et MAISIN J. ? Essai infructueux
de production de cancers de la mamelle chez le Rat
par implantation de diethylstilboestrol. ' ?
tO h. 20 - 10 h. 40 MOSINGER M. ? Sur les effets systematiques, pron-
. feratifs et tumorigenes chez le Cobaye et le Rat, de
substances cestrogenes et cancerigenes.
10 h. 40 - 11 h. D MORICARD R. et GOTHIE S. ? Association vita-
- ,mines-cestrogenes dans la formation des tumeurs
fibreuses chez la femelle de Cobay,e.
"
11 h. D -12 h. D IGLESIAS R. et LIPSCHUTZ A.? Action tumorigene
des cestrogenes endogenes chez le cobaye.
LIPSCHUTZ A. ? Action tumorigene oligodynamique
de rcestrogene et seuils tumorigenes differentiels.
BRUZZONE S., IGLESIAS R., MARDONES E. et
LIPSCHUTZ A. ? La progesterone comme agent
antiluteomateux. '
FUENZALIDA F. ? L'action anti-phosphatasique des
steroIdes dans la proliferation atypique des epithe-
liums uterins.
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Chemische Konstitution und Wirkung pestrogener
und cancerogener Substanzen
H. DRUCKREY (Fribourg, Allemagne).
Die Erfahrung, dass als Lebensinittelzusatze verwendete Substanzen eine
cancerogene Wirkung haben barmen, macht es filr die Entwicklung einer
Prophylaxe des Krebs notwendig, die Gesetzmassigkeiten aufzuklaren, die
dem Zusammenhang zwischen der chemischen Konstitution einer Substanz
und ihrer cancerogenen Wirksamkeit zu Grunde liegen.
Die, vorliegenden experimentellen Erfahrungen ergeben einen engen
Zusammenhang der cancerogenen Substanzen mit Farbstoffen, sodass die
Erkenntnisse der Farbstoff-Chemie (Wizinger, Diltey) auf dies Gebiet ange-
wendet werden konnen.
Danach stellen sich bestimmte aromatische Grundstrukturen als ,r Can-
cerophore heraus, deren cancerogene Wirksamkeit durch die Einfiihrung
a auxOcancerogener a Substituenten verstarkt, durch die a anticancerogener .
Substituenten aber vermindert oder aufgehoben werden kann. Dies Prinzip
scheint ftir viele pharmakologische Wirkungen anwendbar zu sein.
Die I Erfahrung, dass p-Amino-Stilbene und p-Amino-Azobenzole cance-
rogen,1 p-p'-dioxy-Stilbene aber cestrogen sind, fiihrte zu der Vorstellung,
dass p-p'-dioxy-Azobenzol ebenfalls oestrogen sein milsste. Das wird durch
das Experiment bestatigt. Weitere systematische Untersuchungen ergaben
dann, dass die allgemeine Konstitution OH-Aryl (Alkyl)-OH bzw. OH-
Aryl (Alkyl)-COOH oestrogen, die allgemeine Konstitution : Aryl-NH,
bzw. Aryl-N-Alkyl aber cancerogen ist. Dies Prinzip scheint ftir alle wich
tigen Grundsubstanzen von organischen Farbstoffen zu gelten.
Daftir werden Beispiele gebracht. Weiter werden die pharmakologischen
Grundlagen der cancerogenen Wirkung untersucht. Dabei lassen sich die
cancerogenen Substanzen in zwei grosse Gruppen ordnen : die mit lokala
und die mit resorptiver Wirkung. Die Bedeutung dieser Erkenntnisse wird
disk utiert.
Studies on the Induction of Tumors by a
Combination of Carcinogenic Agents and Hormonal Effects
ALEXANDER SYMEONIDIS (Bethesda, U. S. A.).
In considering the factors which lead to the development of cancer, car
cinogenic agents have probably received the greatest attention. The factors
inherent in the cell, and its reaction to other stimuli, have been relatively
neglected. This report presents a series of experiments in which the action
of carcinogenic agents has been studied in the presence or absence of various
hormones. Exemples of these experiments are ;
SERIES I. Mice fed with methylcholanthrene in olive oil were also given
thiouracil.
SERIES IL Rats fed with acetylaminofluorine were also injected with
progesterone.
SERIES III. Rats fed with ortho-amino-azo-toluene were adrenalectomi-
zed. Some of these animals were then treated with desoxycorticosterone.
Induced mammary, thyroid, liver and ovarian tumors are described
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Microscopic studies of the different stages of development of these tumor&
will be presented. Their cellular origin and differentiation under the combi-
ned conditions of hormonal imbalance and carcinogenic ingestion will be'
discussed.
Influence of Environment on the Mammary-Tumor
Incidence in Mice
0. MUHLBOCK (Amsterdam, Hollande).
Litter-mates of virgin females of the Dilute-brown-strain (Little) were
kept in 4 different sort of cages with a different number of animals. So far
as possible all other environmental factors e. g. diet and temperature were
identical. The mammary-tumor-incidence was higher in the cages with a
smaller number of animals; it was highest in the group with each female
in an individual cage. In a second experiment the influence of activity was.
studied by placing a looping-wheel in the cage. In this group the develop-
ment of the ammary-tumors was delayed_ In a third experiment litter-
ma es were ovariectomized at weaning age, implanted with pellets of oes-
tron and progesterone and divided in a group with 50 animals in one cage
and a group with each female in an individual cage. A large difference in
the tumor incidence was found. It is probable that the environmental in-
fluences are acting through the hypophysis.
Essai infructueux de production de cancers de la mamelle
chez le rat par implantation de diethylstilboestrol
F. MEERSSEMAN et J. MAISIN (Liege, Belgique).
Nous avons essaye de produire chez une souche pure de rats ne presen-
tant pas de tumeurs spontanees, des tumeurs de la mamelle suivant les me--
thodes de Dunning Curtiss et Segaloff qui implantent sous la peau de jeunes
animaux des comprimes de cholesterine et de diethylstiboestrol. Nos ani-
maux n'ont jamais presente de cancer ni de la mamelle ni de la vessie, malgre
la presence de calculs dans celle-ci. Par:contre, un nombre important sont
morts d'adenomes de l'hypophyse. Un de ces adenomes pesait 680
mull-
grammes. Nous avons etudie aussi le comportement de ces animaux vis-C-
vis de in genese de tumeurs provoquees par le methylcholantrene.
Sur les effets systematiques, proliferatifs et tumorigenes,
chez le cobaye et le rat, des substances oestrogenes et
cancerigenes. ? Carcinoresistance relative du cobaye. ?
Essais de transmission
MICHEL MOS INGER (Marseille-France et Coimbra, Portugal).
Nos series experimentales, commencees en 1936, concernant les effets
generaux et tumoraux des substances cestrogenes et cancerigenes, se repar-
tissent en groupes :
10 Les substances cestrogenes (dipropionate et benzoate d'cestradiol,
diethylstilboestrol, acide doisynolique, ethinyl-oestradiol) ont ate adminis-
fres, au cobaye, en implantation'ou en injection dans l'huile d'olive, pendant
1 a 37 mois et ont provoque : a) des reticulo-endothelthses a colloldocytes
b) des viscerites sclerosantes multiples sauf des nephrites; c) des reaction.
leiomyocytaires et rhabdomyocytaires d) une conjonctivomatose mul-
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tiple Olbromes, leiomyomes et leiomyofibromes, histiocytomes lipokliques
on giganto-cellulaires, angiomes, lymphocytomes, fibrochondromes) ;
a) une blastomatose multiple avec tumeurs epitheliales et melaniques ;
f) des proliferations et kystes vestigiaires wolffiens, parfois geants ; g) des
embryomes et placentomes ; h) des visceroses kystiques.
2. Les substances, cestrogenes ont.produit chez le rat,, des reticulo-endo-
thelioses d'un type distinct, une conjonctivomatose multiple exceptionnelle
et des sarcomes au lieu d'injection.
3. Les substances cancerigenes (3:4-benzopyrene; 1, 2, 5, 6-dibenzan-
thracene ; 9, 10-dimethyl-1, 2-benzanthracene ; methylcolanthrene) deter-
minent chez le, cobaye, des reticulo-enthothelioses, des 'conjonctivomes
regressifs et, dans certaines conditions, des sarcomes metastasants et trans-
plantables, les transplants etant regressifs. Gertains sont oestrogenes de
meme que la jaune de beurre. Des effets systematiques particuliers ont &le
observes.
4? Ces memes substances eancerigenes, chez he rat, donnent, en injection,
outre des sarcomes, des effets systematiques, conjonctifs et viSceraux.
5? Diverses ergones ont permis des effets stimulateurs, inhibiteurs ou
modificateurs des reactions systematiques at tumorales cestrogene du
cob aye. '
6? Divers types d'extraits visceraux de cobaye ont ete administres au
rat porteur de sarcoma et des diets miodificateurs ou retardateurs ont ete
observes'.
'Association vitarnines-cestrogenes dans la formation
des tumeurs fibreuses .chez la 'femelle de cobaye
R. MORICARD et S. GOTHIE (Paris).
L'action prolongee de substances oestrogenes sur Cobaye a donne lieu a
la production de tumeurs fibreuses genitales et extra-genitales. Nelson
(1937),,Moricard et Cauchoix (1938), Lipschutz (1938), Moricard et Simard
(1940), Ihmes (1945), Jaameri (1946), Mosinger (1947), Nuovo (1948).
Pour expliquer l'inconstance de la production de tumeurs fibreuses nous
avons pense a une action synergique, cestrogenes-vitamines. Nous avons
specialement etudie Faction des cestrogenes sur ,animaux carences et sur-
charges en vitamines A et C. .
1. Animaux normaux non carences, non castres, traites de 1 mgr par
semaine 'de benzoate d'cestradiol pendant 5a, 32 semaines. 13. anirnaux sur
15' piesentent des 'fibrorries' multiples. "
2. Animaux carences en vitarnines A et C : 11-animaux reeevantl, sOit en
implantation soit en injection, de Xcestradiol,(10 a 50 mgr au total)pendant
.8 a 18 semaines : aucun fibrome.
3. Anirnaux surcharges' eir vitamine C (100 mgr 'par semaine) recevant
1 mgr par semaine de benzoate d'cestradiol (2 a 18 .semaines ): 4 animaux
sur 5 ayant des fibromes.
4. Anirnaux surcharges en vitamine A (2 a 5 rhgr par semaine) recevant
1 mgr par semaine de benzoate d'cestradiol pendant 2 a 18 semaines : 1 seu
fibrome rnais plusieurs animaux presentent une fibrose pleurale.
,Interpretation :
, M. Mazoue (1937) avait montre l'action de Facide, ascorbique dans la
genese du tissu fibreux. Ghevallier, Escarras et ,Paillas (1938) ont montre
Faction de la vitamine A sur la fibrose pleurale., Lipschutz obtient des
fibromes regulierement sur des cobayes castres avec des doses tres minimes
et continues d'cestrogenes, 100 y an total. Il discute Faction antifibroma-
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togene des 3 atosteroldes (ii est probable que ses animaux ne sont pas
carences). Pour Mosinger (1945) la presence ou Fabsence d'ovaire n'influence
pas la fibrose d'une facon evidente.
Les substances vitaminiques A et C se comportent comme des transpor-
teurs d'hydrogene, les 3 atosteroides agissent dans le rnaintien d'equilibre
entre les alcools secondaires et les atones correspondantes. Un equilibre
de metabolisme determine est necessaire a l'evolution de la fibromatose sous
l'action prolongee des cestrogenes. C'est probablement par ce mecanisme
que la surcharge en vitamines influence Factivite tumorigene des cestro-
genes.
Action tumorigene des cestrogenes endogenes
chez le cobaye
RIGOBERTO IGLESIAS et ALEXANDRE LIPSCHUTZ
(Santiago, Chili).
Chez des cobayes femelles chatrees, avec autogreffe ovarienne dans la
rate, de petits nodules blanchatres peuvent apparaftre A la surface de cet
organe dans la proximite de la greffe. Ils ont la meme structure que les
multiples nodules fibromateux apparaissant sur la rate chez des cobayes
traites avec de Fcestrogene. On expliquera leur apparition, chez des ani-
maux a greffe ovarienne intrasplenique, par Faction de Fcestrogene pro-
duit dans la greffe meme et ne circulant, de facon continue, que dans la rate.
Plus surprenant et inexplicable est le fait que, chez quelques-uns de ces
animaux, ces nodules furent trouves aussi A la surface de l'estomac, en con-
tact avec la rate et dans les regions voisines de la paroi abdominale.
On trouva, chez ces memes animaux, parfois aussi des formations tubu-
laires dans la rate, soit ala surface ou a une certaine distance de celle-ci.
Ces formations sont revetues d'un epithelium cubolde. Dans un cas, le cana-
lieu& superficiel contenait une substance d'aspect colloidale, faisant penser
A une vesicule thyroldienne. II s'agit probablement de tubes provenant du
rete ovarii qui, dans la greffe ovarienne intrasplenique, devient hyperplas-
tique et kystique. Les tubes ont evidemment acquis la capacite de migra-
tion
Action tumorigene oligodynamique de l'oestrogene
et seuils tumorigenes differentiels
ALEXANDRE LIpSCHUTZ (Santiago, Chili).
1. On provoque, chez la cobaye chatree, avec des quantites rninitnes
d'cestrogenes esterifies ne depassant pas au total 40 gr. injectes dans le cou-
rant de 3 mois, une proliferation atypique des epitheliums uterins : hyper-
plasie kystique de l'endometre, metaplasie et stratification, plis epitheliaux
remplissant les kystes ou la cavite uterine, polypes descendant vers le col et
le vagin (exp. en collab. avec Vargas, Bellodio et autres). Ces quantites sont
en general insuffisantes pour provoquer la reaction proliferative tumorale
mesenchymale de la sereuse abdominale qu'on provoque avec des quantites
plus grandes d'oestrogenes (exp. en collab. avec Iglesias, Vargas et autres).
2. On provoque les mernes phenomenes epitheliaux, ainsi que l'invasion
du myometre par des glandes proliferees atteignant la couche externe Ion-
gitudinale, et des proliferations 'atteignant la profondeur de la tunique du
cervix uterin, par Finjection de quantites plus grandes d'hormones libres
(cestradiol ou cestrone, equilenine) ou hormones synthetiques (stilboestrol),
acides doisynoliques) qui pourtant restent encore insuffisantes pour causer
33
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une reaction fibromyonnateuse (exp. en collabor. avec Rodriguez, Iglesias
et Mardones).
3. Des quantites infinitesirnales d'cestradiol, absorbees d'une maniere
continue a partir d'une tablette sous-cutanee ne contenant qu'1 % de l'hor-
mone et 99 % de cholesterol, se comportent de la merne faeon (exp. en col-
labor. avec Riesco et Tenorio).
4: On observa, dans un lot de cobayes non trait& , sans autres signes d'ac-
tion cestrogene exageree (mamelons et uterus petits), des kystes glandulaires
de I',endometre, des plis epitheliaux et petits polypes. II n'y cut que chez
2 sur 35 de ces animaux, une proliferation tumorale leiomyomateuse insi-
gniflante.
On concluera de ces quatre groupes d'observations convergentes qu'il
existe des seuils tumorigenes differentiels pour les differents tissus aptes a
donner des reactions tumorales. L'existence des sculls tumorigenes diff?
rentiels expliquerait cc fait surprenant ,qu'il s'etablit, chez la femme, une
proliferation tumorale benigne ou maligne qui semble etre due a une action
prolongee d'un cestrogene, sans que celle-ci se montre a d'autres niveaux du
tractus genital.
La progest6rone conune agent antiluteomateux
SILVIO BRUZZONE, RIGOBERTO IGLESIAS, ELVIRA MARDONES
et ALEXANDRE LIPSCHUTZ (Santiago, Chili). ,
-La formation des corps jaunes est stimulee, dans l'autogreffe ovarienne
inttasplenique de 10 cobaye femelle chatree, par l'administration d'cestro-
gene. La luteinisation est contrecarree par l'administration d'cestrogene
La luteinisation est contrecarree par l'administration simultanee de proges:-
teiorie on de desoxycorticosterone. De multiples corps jaunes et une trans-
fornration cc luteomateuse B du stroma ovarien s'etablissent spontanerhent
clang l'autogreffe de la cobaye femelle chatree, environ 10 IBMs apres la
transplantation. Si l'on fait agir de la progesterone pendant environ 3 mois
Cons'ecutifs, les grandes masses de cellules ? luteomateuses du stroma dis-
paraisSent. Les corps jaunes entrent en regression. L'aCtion aritiluteoma-'
tense de la progesterone s'effectue probablement par Yintermediaire de l'hy-
pophyse ; rnais cette conception n'est pas encore definitive, une action locale
du sterolde antilateinisant sm. Fovaire ne i5ouvant etre exclue.?,
L 'action anti-phOsphatasiqUe des steroides,
dans la proliferation atypique des epitheliums uterins
FLORENZIO FUENZALIDA (Santiago, Chili).
, ? ?
?Ii se produit une augmentation considerable de la phosphatase alcaline
danS41a muqueuse uterine de la cobaye 0 laquelle on a adrninistre de l'ces-
trogene pendant Wusieurs mois pour provoquer une proliferation &pith&
liale atypique. Cette augmentation de la phosphatase de la muqueuse ne se
prodnit pas si Ton administresimultanement de la progeSterone, chi propio-
nate de testosterone ou de la dihydrotestosterone. '
? ,
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AMPHITHEATRE ? 2 A ? (RICHELIEU)
Mardi matin 18 juillet 1950 (de 9h. a 12 h.)
- SECTION : CANCERS ET HORMONES
Presidents: R. KORTEWEG et A LIPSCHUTZ
9 h. - 9 h. 20 ENGEL L. L., NATHANSON I. T., EKMAN G. et
SCHINKET M. ? The urinary excretion of ketoste-
roids and steroid alcohols in cancer patients.
9 h. 20 - 9 h. 40 EVANS H. M. ? Neoplasms in rats treated with pitui-
tary growth hormone.
-9 h. 40- 10 h. WOOLLEY G. W. ? 11-Ox3fgenated adrenal cortical
steroids and cancer.
10 h. - 10 h. 20 PENCHARZ R. ? An experimental study of the
growth of intrasplenic ovarian grafts and their trans-
formation into tumors.
10 h. 20 - 10 h. 40 VAN LANCKER J. et MAISIN J. ? Greffes d'ovaires
et de testicules dans in rate d'animaux castres.
10 h. 40 - 11 h. GARDNER W. U. Experimental ovarian tuniorige-
nesis in laboratory animals.
11 - 11 h. 20 GARDNER W. U.-- Testicular interstitial cell tumors
in mice given tri-anisyl-chlore-ethylene.
11 h. 20 - 11 h. 40 KORENCHEVSKY V. ? Spontaneous development
of metahyperplasias and adenoma-like structures in
senescent rats.
11 h. 40 - 12 h. KORENCHEVSKY V. ? Cooperative effects of the
processes of ageing, and over-stimulation with horT
mones in producing adenoma-like structures or;
adenomas in senesCent rats. ,
?
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The Urinary Excretion of Ketosteroids and Steroid
. Alcohols in Cancer Patients
LEWIS L. ENGEL, IRA T. NATHANSON, GLADYS EKMAN
and MARION SCHINKET (Boston, U. S. A.).
Development of a colorimetric method for the estimation of total steroid
alcohols has added a useful tool for the study of the urinary excretion of
steroid compounds. Preliminary experiments in normal subjects and sui-
table patients have indicated that the major source of these compounds is
the adrenal cortex but that the gonads may make a substantial contribu-
tion.
The administration of progesterone to cancer patients and control pa-
tients with rheumatoid arthritis is followed by an increased excretion of
total steroid alcohols and non-ketonic alcohols. Similarly, after the admi-
nistration ,of dehydroepiandrosterone to cancer patients there is a rise in
non-ketonic alcohols and in ketosteroids. However, in five of six female
patients with breast carcinoma, the administration of testosterone propio-
nate is, followed by a rise in the excretion of ketosteroids but a dramatic
fall in the excretion of non-ketonic alcohols. In one patient with prostatic
carcinoma treated with testosterone, there was a slight increase in the
excretion of non-ketonic alcohols, while in three patients with rheumatoid
arthritis treated similarly the response was irregular.
The significance of these changes in regard to cancer is not clear but it
appears that testosterone is metabolized largely to ketonic compounds and
also depresses the endogenous production of non-ketonic alcohols by the
adrenal cortex. The metabolic pathway of dehydroepiandrosterone may be
partly in the direction of non-ketonic alcohols and it may exert a smaller
effect on the endogenous production of steroid alcohols by the adrenal cor-
tex.
Neoplasms in Rats Treated with Pituitary Growth Hormone
HERBERT M. EVANS (Berkeley, U. S. A.).
Many neoplasms of various types occurred in plateaued female rats recei-
ving large amounts of_pituitary growth hormone for periods up to ;485 days.
Very few tumors occurred in the controls receiving similar amounts of albu-
men for the same length of time. Neoplastic and hyperplastic changes were
frequently observed in the lungs, adrenal medullas, and reproductive organs.
Lymphosarcomas of the lung were present in almost one-half of the rats.
These lesions apparently developed in hyperplastic peribronchial lymphoid '
tissue. All of the rats showed hyperplasia and hypertrophy of the adrenal
medulla. In two-thirds of the rats there were either large pheochromocyto-
mas or focal areas of transformation into neoplasms of this type. Fibro-
adenomas of the mammary glands were the most common tumors noted
in these'rats and were usually multiple. Tumors of the ;ovaries apparently
arising from preexisting structures (small follicles and pseudo-testicular
tubules) were also encountered. Comparable lesions have not occurred in
controls receiving albumen or in hypophysectomized rats receiving large
amounts of growth hormone.
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11-Oxygenated Adrenal Cortical Steroids and Cancer
by George W. WOOLLEY (New-York, U. S. A.).
Evidence is already at hand that cortisone and adrenal cortical extracts
influence lymphoid tissue and certain lymphoid tumors. A C T H, presu-
mably through stimulation of adrenal cortical function, causes regression of
lymphoid tumors in man. This report presents evidence that in addition to ,
cortisone, such 11-oxygenated compounds as 17-hydroxycorticosterone, --
21-desoxy cortisori6; and 17-desoxycortisone,.modify and aid in the control
of expeiimental muse tumors. -
An Experimental Study of the Growth of Intrasplenic
Ovarian Grafts and Their Transformation into
Tumors
RICHARD PENCHARZ (Stanford, U. S. A.).
If an ovary of a rat is transplanted into the spleen of a gonadectomized
animal, the ovarian graft undergoes a marked hyperplasia and is slowly
converted into a tumor. The resulting growths may take one of three form :
1) luteoma, 2) thecoma, and 3) granulosa cell tumor. Of the three, the gra-
nulosa cell growth is the slower developing, and appears less frequently than
the thecoma or luteoma. Usually, all three types of tissues can be identified
in the same growth.
Intrasplenic ovarian grafts fail to grow in the normal animal with intact
ovaries. Such grafts remain viable though markedly reduced in size. Remo-
vallof the intact ovaries is followed by the resumption of growth of the atro-
phic intrasplenic ovarian graft. The time interval between the original trans-
plantation of the ovary into the spleen and subsequent removal of the intact
ovaries do not modify the later transformation of the graft into a tumor. -
fiats bearing tumors in their spleens may or may not show evidence of
estrogenic activity. The presence of freely circulating estrogenic hormones
in the peripheral circulation does not interfere with the growth of the tumor.
The tumdr does not grow' in the hypophysectomized animal, and the fully
established tumor suffers atrophy following removal of the pituitary. Efforts
to transplant the tumor have not proved successful.
Histological findings will be illustrated by lantern slides.
Greffes d 'ovaires et de testicules dans la rate
d 'animaux castres
J. Van LANCKER et J. MAISIN (Louvain, Belgique).
Suite aux experiences de M. S. Biskind et G. R. Biskind chez le rat ainsi
que celle de H. Min Sin Li et W. U. Gardner chez la souris, nous avons voulu
reporter leurs experiences chez une race pure de rats entretenue a l' Institut
du Cancer de Louvain depuis plus de 10 ans. Depuis cette ?que sur plu-
sieurs milliers de rats observes, nous n'avons jamais constate de cancer
spontane. Cent rats castres des deux sexes ont ete implantes d'ovaires de
rats nouveau-nes dans la rate. Environ 1/3 des animaux ainsi greffes ont
presente une tumeur de la rate. Ces tumeurs sont de vrais neoplasmes, Hs
out une teinte blanc-nacre de volume variable suivant Page de la tumeur
? 37 ?
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11-Oxygenated Adrenal Cortical Steroids and Cancer
by George W. WOOLLEY (New-York, U. S. A.).
Evidence is already at hand that cortisone and adrenal cortical extracts
influence lymphoid tissue and certain lymphoid tumors. A C T H, presu-
mably through stimulation of adrenal cortical function, causes regression of
lymphoid tumors in man. This report presents evidence that in addition to ,
cortisone, such 11-oxygenated compounds as 17-hydroxycorticosterone, --
21-desoxy cortisori6; and 17-desoxycortisone,.modify and aid in the control
of expeiimental muse tumors. -
An Experimental Study of the Growth of Intrasplenic
Ovarian Grafts and Their Transformation into
Tumors
RICHARD PENCHARZ (Stanford, U. S. A.).
If an ovary of a rat is transplanted into the spleen of a gonadectomized
animal, the ovarian graft undergoes a marked hyperplasia and is slowly
converted into a tumor. The resulting growths may take one of three form :
1) luteoma, 2) thecoma, and 3) granulosa cell tumor. Of the three, the gra-
nulosa cell growth is the slower developing, and appears less frequently than
the thecoma or luteoma. Usually, all three types of tissues can be identified
in the same growth.
Intrasplenic ovarian grafts fail to grow in the normal animal with intact
ovaries. Such grafts remain viable though markedly reduced in size. Remo-
vallof the intact ovaries is followed by the resumption of growth of the atro-
phic intrasplenic ovarian graft. The time interval between the original trans-
plantation of the ovary into the spleen and subsequent removal of the intact
ovaries do not modify the later transformation of the graft into a tumor. -
fiats bearing tumors in their spleens may or may not show evidence of
estrogenic activity. The presence of freely circulating estrogenic hormones
in the peripheral circulation does not interfere with the growth of the tumor.
The tumdr does not grow' in the hypophysectomized animal, and the fully
established tumor suffers atrophy following removal of the pituitary. Efforts
to transplant the tumor have not proved successful.
Histological findings will be illustrated by lantern slides.
Greffes d 'ovaires et de testicules dans la rate
d 'animaux castres
J. Van LANCKER et J. MAISIN (Louvain, Belgique).
Suite aux experiences de M. S. Biskind et G. R. Biskind chez le rat ainsi
que celle de H. Min Sin Li et W. U. Gardner chez la souris, nous avons voulu
reporter leurs experiences chez une race pure de rats entretenue a l' Institut
du Cancer de Louvain depuis plus de 10 ans. Depuis cette ?que sur plu-
sieurs milliers de rats observes, nous n'avons jamais constate de cancer
spontane. Cent rats castres des deux sexes ont ete implantes d'ovaires de
rats nouveau-nes dans la rate. Environ 1/3 des animaux ainsi greffes ont
presente une tumeur de la rate. Ces tumeurs sont de vrais neoplasmes, Hs
out une teinte blanc-nacre de volume variable suivant Page de la tumeur
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716 days. About 80 per cent of the mice of this stock given estradiol ben
zoate have pituitary tumors.
Studies in progress are designed to determine whether the differences in
the response is due to quantitative factors.
Spontaneous Development of Meta-Hyperplasias
and Adenoma-Like Structures in Senescent Rats
V. KORENCHEVSKY (Oxford, Grande-Bretagne).
In senescent rats, of the breed used at the Unit, in the thyroid, adrenals
pancreas, thymus and liver, certain- meta-hyperplasias and, more rarely,
adenoma-like structures occur from the age of about 20 months. Special
histological features of these meta-hyperplastic structures and the frequency
Of their occurrence, are recorded. Their significance is connected with the
fact that in human beings from such structures adenomas or adenocarci-
nomas could easily be developed.
Cooperative Effects of the Processes of Ageing,
and Over-Stimulation With Hormones in Producing
Adenoma-Like Structures or Adenomas in Senescent Rats
V. KORENCHEVSKY (Oxford, Grande-Bretagne). -
- The treatment of senescent rats with hormones of the anterior hypophy-
sis, sex and thyroid hormones and desoxycorticosterone acetate was followed
by the appearance of, or enhancement in the development of pronounced
degrees of adenoma-like structures, or adenomas. These formations were
found in the thyroid, parathyroid, adrenals; pancreas, thymus and liver.
Their special features distinguished them, in a certain way, from spon-
taneous meta-hyperplastic processes.
. Description is given of these special features with demonstration by mi-
crophotographical slides.
In their production and development the cooperative effects of the pro-
cesses of ageing and overstimulation with hormones is instrumental.
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AMPHITHEATRE a 2 A)) (RICHELIEU)
Mercredi matin 19 juillet 1950 (de 9 h. a 12 h.)
SECTION: CANCERS PROVOQIJES
Presidents: C. AIM et F. BANG
Ii. - 9 h. 20 HORNING E. S. ? Rapid induction of prostatic
tumours in mice.
9 h. 20- 9 h. 40 LASNITZKI I. C.? Precancerous changes induced by
methylcholantrene in Mouse prostrates grown in
vitro.
9 h. 40 - 10 h. ? STEWART H. L. ? The lesions induced by intra-
mural injection of 20-methylcholanthrene at two
sites in the glandular stomach of the Rat.
10 h. -10 h. 20 SAXEN E., EKWALL P. et SETALA K.? Squamous
cell carcinoma of the forestomach in mice following
oral administration of 9,10-dimethy1-1,2-benzanthra-
cene solubilized in aqueous solutions of association
colloide.
10 h. 20 - 10 h. 40. ? DANTCHAKOFF V. ? Effets du Methylcholan-
threne injecte au cobaye gravide.
10 h. 40 - 11 h. VAN DER SCHUEREN (G.) et DEBIE (F.). ? Le
comportement specifique de differents organes
d'un hydrocarbure cancerigene.
- 11 h. 20 HOCH-LIGETI (C.) et RUSSELL (D. S.). ? Primary
Tumours of the Brain in Rats fed 2-acetylaminofluo-
rene.
11 h.
11 h. 20 - 12 h. YUN (I. S.).? The Effect of the Spleen on the Produc-
tion of Hepatic Tumors in Animals following the
Introduction of 20 - Methylcholanthrene into the
Liver.
? Effets of Splenic Extract Injection on the Deve-
lopment of Tumors in the Skin of the Mice by 20-
Methylcholanthrene.
? Influence of the spleen on.the induction of tu-
mors in mice with subcutaneously injected 20
methylcholanthrene.
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Rapid Induction of Prostatic Tumours in Mice
E. S. HORNING (Londres, Grande-Bretagne).
Rapid induction of prostatic tumours is achieved in pure line mice by
impregnating fragments of prostatic epithelium with a suitable carcinogen
and in some instances with a hormone and grafting the whole subcuta-
neously in host mice of the same age, sex and strain. Transplantable glandu-
lar carcinomas of the prostate gland can be readily induced by this tech-
nique. The factors upon which homologous subcutaneous grafts are depen-
dent for their successful survival and growth in host animals will also be
discussed.
Precancerous Changes Induced-by Methylcholantrene
in Mouse Prostates &own:TR-Vitro
I. LASNITZKI (Cambridge, Grande-Bretagne).
Prostate of young mature mice were grown in watchglasses in a medium
of chick plasma, chick embryo extract and human serum. In the experimen-
tal series methylcholantrene was added in a concentration of 2 y per cern.
of mediums. As a rule new alveoli are formed at the periphery of the gland
while in the centre the glandular epithelium underwent some degeneration.
In the control cultures the alveoli were lined by one layer of healthy cuboidal
epithelium composed of regularly arranged cells of even shape and size;
nlitosis, however, is rare.
The experimental cultures were grown in the medium containing methyl-
cholantrene for nine days and then transferred to a normal medium and
fixed at intervals after removal of the carcinogen. These cultures showed
also desquamation of the secretory epithelium in the centre but conside-
rable proliferation of the epithelium in the periphery. Mitosis was plentiful.
This growth activity caused a multiplication of the epithelial layers lining
the alveoli. Often papilliform formations were seen which sometimes occlu-
ded the lumen. In the later stages some of these epithelial proliferations un-
derwent squamous metaplasia.
Methylcholantrene thus seems to interfere directly with the normal pro-
cess of differentiation. In the concentration used it promotes epithelial
growth and mitosis.
Grafts of such cultures into mice of the same strain are being made in
order to test whether the induced changes are permanent and lead to mali-
gnancy.
The Lesions Induced by Intra-Mural Injection
of 20-Methylcholanthrene at two Sites in the Glandular
Stomach of the Rat
HAROLD L. STEWART (Bethesda, U. S. A.).
Young adult rats received an injection of methylcholanthrene at each of
two sites in the wall of the glandular stomach, one near the pyloric ring, the
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.other near the limiting ridge. The pathological changes evoked at each site
will be described. The results of the transplantation of each injection site
subcutaneously to mice to determine the persistence of the carcinogenic
hydrocarbon at the site of injection will be presented.
Squamous Cell Carcinoma of the Forestomach
in Mice Following Oral Administration
of 9,10-Diniethy1-1,2-Benzanthracene Solubilized
in Aqueous Solutions of Association Colloids
ERKKI SAXEN, PER EKWALL and KAI SETALA
(Helsingford, Finlande).
We Wish by means of these experiments to throw some light on the ques-
tion whether the stability or instability in the stomach of the association
colloid micelles and their related power of solubilizing the carcinogen in
any way affect the penetration of the carcinogen into the gastric wall and
whether under these conditions the carcinogen is capable of producing tu-
mours in the stomach or in other organs.
The carcinogen was solubilized in aqueous solutions of sodium oleate,
sodium cholate, sodium myristyl sulaphate and an alkyl aryl polythen al-
cohol (Triton N). Triton N is non-ionic association colloid the others are
anionic'. In Triton and sodium myristyl sulphate solutions the carcinogen
will remain solubilized in the micelles even though the pH value is low. ,The
micelles in oleat solution are not stable below WI 7-8.
The solution was introduced direct into the stomach of the animals by
means of a thin polythene cannula.
? We have found that when the carcinogen was solubilized in sodium cho-
late, sodium myristyl sulphate and Triton N, it penetrates into the wall of
the forestomach as well as into that of the glandular stomach. In sodium
oleate solutions this could not be demonstrated.
Squamous cell carcinomata of the forestomach could be induced :with all
the different solutions, but the carcinogenic activity was much ',lower in
sodium oleate solutions. The time which elapsed before the incidence of the
first carcinoma varied from 115 to 215 days corresponding to only 1:3-
1,65 mg of 9,10-dimethyl 1,2-dibenzanthracene.
It seems possible that the action of carcinogenic hydrocarbons in aqueous
?solutions of association colloids greatly depends on the nature of the col-
loid. The acid stability of the colloid solutions seems to be of great value.
Effets du methylcholanthrime injecte au cobaye gravide
VERA DANTCHAKOFF (Lausanne, Suisse).
Le derangement, responsable du pouvoir de proliferation precipitee et
illimitee de la cellule cancereuse, nous echappe encore. Seul le fait, qu'a
,partir des agents les plus divers, des cellules de nmintes especes acquierent
une capacite d'intensifier? leurs reaCtions cevitales- d'abreger lent's? cycles
?mitotiques et de les renouveler incessamment, ,temoigne !d'un chanqement
profond ,d'un facteur special .et cmrunun a toutcis .les cellules. Devant les irri-
tantes difficult& qu'il y "a?k cloinitier une situation inconnue, une possibilite
kl'intervenir dans la propagation du Mau prend tine valeur particuliere.
Des conditions speciales, propres aux Mammiferes, pourraient influencer
la transmission du cancer. Les.ovules d'une.femelle porteuse de substances
cancerigenes, restent-ils. indemnes ? Et son fruit, serait-il Isoumis, comme
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tout autre de ses tissus, aux effets des substances nocives, si toutefois celles-
ci traversent le placenta ? C'est le probleme que je me suis pose.
Cobayes, methylcholanthrene, benzopyrene, embryons traites directement
-ou soumis A une gestation compromise par un traitement de la mere gravide,
m'ont servi de points d'approche.
Le traitement direct, inoffensif pour l'embryon, amene sa mort, si c'est une
substance cancerigene qui lui est administree. Des injections a la mere provo-
quent des avortements frequents : Quelque chose doit bien passer a tracers le
placenta.
Des 16 cobayes traitees, 2 ont developpe des sarcomas des glandes mam-
maires, 8 mois apres la premiere injection, dose totale inject& ? 50 mgr;
5 mgr par injection, A 5 jours d'intervalle, durant deux gravidites espacees
de 3 mois ; injections faites A 3-4 cm de la glande. 11 animaux out avorte ;
plusieurs de leurs fruits etaient maceres. Un seul animal 'a mis au monde
2 petits, morts bientot apres la naissance. 4 animaux furent sacrifies et leurs
5 fcetus A terme ont fait l'objet de mes etudes.
Demonstration de leurs organes, dont les coupes de la rate presentent :des
nappes uniformes de cellules-meres de la lignee hemopoletique. Tous les
details pris en consideration, les resultats obtenus semblent indiquer que
chez le Cobaye, le placenta n'est pas une barriere infranchissable a des sub-
stances qui, chez la mere et le fruit, provoquent des alterations semblables.
Le comportement specifique de differents organes vis-a-vis
d'un hydrocarbure cancerigene
G. VAN DER SCHUEREN at FR. DEBIE (Louvain, Belgique).
Trois differents organes sont comparativement soumis a l'action du me-
thylcholanthrene. Introduit dans la cavite thoracique de la souris, le me-
thylcholanthrene exerce une influence cancerigene locale notoire.
Au contraire, l'application de methylcholanthrene sur la muqueuse vagi-
nab e rectale n'est jamais suivie de proliferation neoplasique dans cette
tunique. L'administration intrarectale de methylcholanthrene chez la souris
a provoque deux fois un leiomyosarcome du rectum at deux autres tumeurs
. A distance. ?
L'injection intravaginale un nombre considerable de souris n'a jamais
reussi a produire une seule tumeur du tractus genital. Toutefois de nom-
breuses tumeurs apparurent a distance, parmi lesquelles est releve un haut
pourcentage abselu de cancers mammaires chez une race d'animaux sans
histoire hereditaire A ce point de vue.
Cette specificite carcinogene du methylcholanthrene pour le tissu mam-
make ne se manifesto, pas chez le rat. Cat animal resiste parfaitement A de
fortes doses de' methyleholanthrene, injectees par la voie Vaginale durant
une tres longue periode, sans presenter de turneur en aucun endroit du corps.
Cependant les modifications du, cycle genital temoignent de la resorption
du methylcholanthrene.
PriMary, Tumours of the Brain in Rats
fed 2-acetylamino-fluorene
?
C. HOCH-LIGETI and D. S. RUSSELL (Londres, ;Grande-Bretagne).
? A glioma described by Vazquez-Lopez' (1945), which was obtained in an
albino rat after feeding 2-acetylamino-fluorene, is-the only previous known
instance of a tumour of the central nerVous system, produced by feeding a
carcinogen. In the present experiment 50 rats were fed on a diet containing
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0,07 2-acetylaminofluorene; 30 of them received a supplement of fresh
milk daily (10 ml. per rat). Fresh milk has been found to protect the liver
from the carcinogenic activity of p-dimethylaminoazobenzene (Hoch-
Liget!, 1946). Although milk did not prevent tumour production by 2-ace-
tylaminofluorene, the site of the tumours and the longevity of the rats
seemed to be influenced. 2 primary tumours of the brain were found in this
group and one in the group of rats not receiving milk. The first two tumours
were glioblastomas, the third was a meningioma. The meningioma was trans-
planted intracranialy into four rats. In one rat, killed 5 weeks after the
transplantation, a small nodule a meningioma adhering to the dura was
present.
1
The Effect of the Spleen on the Production of Hepatic
Tumors in Animals following the Introduction
of 20-Methylcholanthrene into the Liver.
IL SUN YUN (Seoul, Coree).
/ In 1940, Shear and Stewart concluded that the failure to obtain une-
c quivocally induced tumors of the liver in a considerable proportion of the
? . mice indicates that the liver is refractory to the carcinogenic action of the
hydrocarbone. But we have confirmed by several experiments that the
1 ? ?s ' effect of the spleen on the development of tumor growth is noticeable.
? The animal, 90 adult rabbits, 60 C3FT strain, 90 adult strain A mice were
used. 20-Methylcholanthren was administrated after 2 months of removal
- of the spleenin experimental group, as a control, other animals were appli-
?
cated the same dosis of 20-Methylcholanthrene by several techniques.
?- I : In the experimental animals were injected of the solution lof methyl-
.-cholanthrene that lived for more than 3 months occured the hepatic tu-
t mors. As a control there a slight increase in fibrous tissue and cirrhotic
k ?
?? - change.
II : A cotton thread in a sesame oil was inserted into liver. The animals
that lived for more than 3 months in experimental group occured hepatoma
in all cases.
k
mals that removed the spleen. In experimental group survived for 4 months
III : 20-Methylcholanthrene pellets were inserted into the liver in ani-
mals that
hepatoma in all cases. In control animals there was a localized area
of cirrhosis and invadea adenocarcinoma in few cases.
-Effects of Splenic Extract Injection on the Development
of Tumors in the Skin of the Mice
by 20-Methylcholanthrene
IL SUN YUN (Seoul, Coree).
1
In the present investigation, we have since found that following is an
account of the skin changes seen in the mice which removed the spleen
reacting rapidly to the carcinogen. In a series Of 0 mice Of Strain A, 30 C3F1
strain a 0,6 per cent solution of methylcholanfhrene in benzen and olive
oil was applied. Half of animals which removed the spleen were injected the
splenic extract 3 times a week.
A single application of methylcholanthrene to a large skin area in control
mice produced papilloma and even carcinomas.
The result which is in agreement with observation of other investigators
in a different strain of mice.
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It should be noted that under the experimental mice were injected the
splenic extract diminished the development of tumor in the skin.
As a result, we confirmed that the splenic extract showed the inhibitory
effect on the development of tumors in mice with painted methylcholan-
threne.
Influence of the Spleen on the Induction of Tumors
in Mice with Subcutaneously injected
20-Methylcholanthrene
IL SUN YUN (Seoul, Coree).
There are only few reports on the successful production of malignant
tumors in mice following administration of hydrocarbons, subcutaneously.
The impression from the literature, therefore is that neoplasms can be
induced in mice following injection of carcinogenic hydrocarbons indicate
the low incidence and the long latent period.
Twenty-eight C3I-1 strain, 30 strain A mice were injected in the right
axilla with 20-Methylcholanthrene dissolved in olive oil. Before the
injection half of animals were removed the spleen. In an average of 14 weeks
after the injection of methylcholanthrene in the mice were removed the
spleen had definite masses which were circumscribed and fairly movable
which continued to increase in size. During the following 28 weeks after
injection in controls, developed tumors at the site of injection. The growth
rate of the tumors varied widely. In the animals were removed the spleen
that over 14 weeks developed liposarcomas and fibrosarcomas at the site of
injection. But in average of 28 weeks after injection in control, the tumors
became palpable. The tumors metastasized to the lung. There was higher
differences in susceptibility, under the conditions of experimental mice
more than the control mice for induced the tumors with subcutaneously
injected 20-methylcholanthrene.
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AMPHITHEATRE a 2 A,, (RICHELIEU)
Jeudi matin 20 juillet 1950 (de 9 h. a 12 h.)
SECTION : CANCERS PROVOQUES
Presidents : L. KREYBERG J. L. NICOD
9 h. ? - 9 h. 20 SMITH W. E., SUNDERLAND D. A. et SUGIURA K.
? Experimental analysis of the carcinogenic activity
of certain petroleum products.
9 h. 20 - 9 h. 40 BAKER K.? Carcinogenic activity of 3 : 3'-dihydroxy
benzidine.
9 h. 40 - 10 h. ? CANTERO A. ? Studies of chemical carcinogenesis
and properties of precancerous cirrhotic liver in rats
fed p-dimethylaminoazobenzene.
10 h: ? -10 h. 20 MUELLER G. C. et MILLER J. A.? The metabolism
of 4-dimethyl aminobenzene and related carcinoge-
nic amino dyes by rat liver homogenates.
10 h. 20 - 10 h. 40 ? BRACHETTO-BRIAN (D.). ? Histogenese des tu-
meurs du poumon induites par Furethane (ethyl-
carbamate).
ZAJDELA F. et BUU-HOI N. P. ? Activite canceri-
gene de nouvelles benzacridines angulaires.
10 h. 40 - 11 h.
11 h. ? - 11 h 20 SISSONS H. A. ? Bone sarcomas produced experi-
mentally in the rabbit, using compounds of beryllium
11 h., 20 - 11 h. 40 WARTMAN W. B., SHUBIK P., HILL W. T., REEB
B. B., STANGER D. W. and RIEGEL B. ? Delay
of methylcholanthrene carcinogenesis by 1, 2, 5, 6-
dibenzofluorene.
11 h. 40 - 12 h. ?
SALAMAN M. H. ? Histology of co-carcinogenesis.
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Experimental Analysis of the Carcinogenic Activity
of Certain Petroleum Products
WILLIAM E. SMITH, DOUGLAS A. SUNDERLAND,
and KANEMATSU SUGIURA (New York, U. S. A.).
As part of the preventive medical program of a petroleum company, we.
conducted tests for carcinogenic activity on approximately 400 samples
from refinery, laboratory and wax works operations. Each sample was tested
by painting on a group of 30 mice.
Oils from Fluid Catalytic Cracking Process : Carcinogenic activity was
found only in fractions having a final boiling point above 700?F. The carci-
nogenicity of the most potent oils studied was reduced in proportion to dilu-
tion with non-carcinogenic oils. Blends containing not more than 10 % of
potent oils elicited only occasional tumors and these were benign.
Waxes : Unrefined petroleum waxes elicited cancers late and infre-
quently, but their aromatic extracts were very active. The hazard in wax
works thus appears to be associated with the aromatic compounds in unpu-
rifled wax and not with the paraffine.
Colorado Shale Oil : Production of oil from shale has not yet been deve-
loped commercially in America. Samples obtained from an experimental
fluidizing process induced occasional benign papillomas but few cancers.
3
Carcinogenic Activity of 3 : 3' Dihydroxy Benzidine
KENNETH BAKER (Manchester, Grande-Bretagne).
I. Benzidine has not previously been shown to be carcinogenic experi-
mentally although* clinically it has been accepted as a cause of papilloma'
of the bladder amongst dye workers.
II. It is known that Benzidine is oxidised within the body and that it
forms a dihydroxy-diamino-diphenyl.
III. A dihydroxy-diamino-diphenyl with a melting point of 136/1380G
has been isolated from urine of workmen manufacturing benzidine.
, IV. This compound was identified by means of chromatograph tech-
nique against a synthesised control of 3 : 3' dihydroxy-4 : 4' diamino-diphe,
nyl.
- V. 36 mice (Delph males) were split into 3 groups of 12. Group A received
the metabolite in olive oil BP, Group B received olive oil only. Group C
:were blanks.
VI. Tumours found in, each group :
- Group A. Group B. Group C.
9 1
_ VII. The incidence of spontaneous tumours in the strain of mice -used
throughout these experiments is 6=8 %. 1
VIII. One may conclude that Benzidine will not produce tumours of the
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bladder experimentally but that this may be a condition of the experiment.
IX: 3 : 3' dihydroxy 4 : 4' diamino diphenyl, a primary metabolite of
Benzidine, seems to give rise to far greater activity within the bladders of
experimental animals.
X. A causative agent of the eBenzidine Tumour in the dye worker may
be the metabolite isolated (or an isomer) rather than the benzidine base.
XI. Further work with a view to isolating and investigating isomers of
the 3,: 3' dihydroxy benzidine is proceeding.
Studies of Chemical Carcinogenesis and Properties
of Precancerous Cirrhotic Liver
in rats fed p-dimethylaminoazobenzene
ANTONIO CANTERO (Montr?, Canada).
Our, previous work has shown that dimethylaminobenzene when fed to
rats induces in the liver, at 120 days enzymatic patterns, which are most
suggestive of neoplasia.
A high anaerobic glycolysis, a reduction in cytochrome C, in riboflavin
and catalase, seem initiated in precancerous stage. Proposed to further
investigate in what manner aminoazo dye induces gross changes in the
intracellular composition of the rat liver which are continued in an exacer-
bated 'form in the neoplasic state. Enzymatic activities in fractions of pre-
cancerous cirrhotic liver and in hepatoma were compared.
Experiments are being carried ?out in two separate groups. ? Wistar
white rats : 1) fed the aminoazo dye with a semi synthetic protected diet;
2) a cooked polished rice diet. For each fractionation the livers of 3 rats
are perfused in situ with 0.14 M. Nacl. and then homogenized in 0.88 Mt su-
crose.
The Ilarge and small granules are sedimented in a Servall Ultracentrifuge
rotor (SS 2 Vacuum type) A force of 19,000 x g. for 10 minutes, sediments
the large granules and 45,000 g for 2 hrs. sediments the small granules.;
Distribution of Cytochrome C, succinoxidase, riboflavin and catalase
were carried out in the whole homogenate, large granules, small granules
and supernatant fluid.
As can be noted by the following table, which include part of our results,
to date, that at the precancerous cirrhotic stage, as well as the hepatoma
stage, the Cytochrome linked respiratory enzyme are an integral part of
the large granules, but with a marked diminution in the neoplastic state,
which may mean that the exagerated alterations in the intracellular com-
position under the action of the aminoazo dye, since in the cells it affects,
we know now also desoxy & ribonuclei acid in the various components.
As regards the succinoxidase activity, not sufficient variations were found
between the large & small granules to warrant presently a definite conclu-
sion. ,
1) So fnr, of the enzyme systems examined none was found to be associa-
ted with the small granules in significant amounts.
2) Riboflavin distribution was bound with the large granules and in pro-
cess of liver becoming neoplastic, changes appeared more marked in the
nuclear fraction.
3) Catalase appeared distributed in the supernatant fraction, with very
little or no catalase in the nuclear fractions in precancerous stage and hepa-
toma stage.'
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The Metabolism of 4-Dimethylaminoazobenzene
and Related Carcinogenic. Aminoazo Dyes
by Rat Liver Homogenates
GERALD C. MUELLER and J. A. MILLER (Madison, U. S. A.)
The hepatic carcinogen 4-dimethylaminoazobenzene and ;related ami-
rioazo carcinogens are subject to at least three metabolic reactions in the
intact rat : reductive cleavage of the azo linkage, demethylation of the
N-methyl groups, and hydroxylation, principally at the 4'-position. Each
of these reactions has now been observed in properly fortified rat liver homo-
genates and studies have been made on the nature of two of these reactions.
The reductive cleavage of these dyes to yield the corresponding mono-
phenyl amines has been demonstrated to be catalyzed by a 'flavoprotein
which contAins riboflavin-adenine-dinucleotide as the prosthetic group.
Reduced triphosphopyridine nucleotide is required specifically as the elec-
tron donor in this reaction. The cleavage enzyme is found only in the parti-
culate fractions of the liver cells, with the highest concentration being found
in the small granules or microsomes.
Demethylation of the dimethylamino group has been found to occur in a
stepwise manner. The removal of the first methyl group to yield the mono-
methylaminoazo dye proceeds slowly while the demethylation of the mono-
methyl dye takes place rapidly in homogenates. The latter demethylation
requires fortification of the reaction mixture with triphosphopyridine
nucleotide and adenosinetriphosphate.
The implications of these in vitro findings in reference to the problem of
azo dye carcinogenesis will be discussed.
Histogenese des tumeurs du poumon induites
2 par Purethane ( Ethyl Carbamate)
DOMINGO BRACHETTO-BRIAN (Buenos-Aires, Argentine).
1. Nous employons la souris blanche, souche suisse, 2 mois, des deux
sexes, de notie elevage favorable par sa ties basse incidence en tumeurs
spontanees du poumon (1 a 2 %) et par sa notable sensibilite a l'urethane
,(98-100 ; injection unique, intraperitoneale, de 1 ml. sol. urethane 10 %
x 100 g de poids : sacrifice par section bulbaire.
2. Des 24 a 72 heures, on trouve des alterations dans la paroi alveolaire ;
-discrete hyperhemie et polynucleose ; necrose des cellules (75 %), princi-
palement des cellules alveolaires." ' ' ? ?
Apres 8 jours, hypertrophie de la Paroi alveolaire, due en grande partie
l'augmentation numerique des .cellules de revetement, avec de tres rares
mitoses ; predominance de pycnoses. Les cellules parietales mieux conser-
Nees.
A 35-45 jours, recuperation partielle de l'epaisseur de la paroi alveolaire ;
es pycnoses reduites a 33 %. 11 y a de nombreuses cellules cubopolyedriques,
basophiles et a grand noyau, qui se,rapportent aux cellules alveolaires.
C'est alors qu'apparaissent des tumeurs developpees dans le parenchyrrie
alveolaire, riches en cellules sus-dites. L'examen de la peripherie ,des tu-
meurs montre ces cellules l'une ?t?e l'autre, comae un ruban qui s'en-
roule ensuite pour former la turneur.
3. Les faits exposes permettent d'interpreter ainsi, l'histogenese : a) L'u-
rethane, tout en s'eliminant par le poumon y exerce une, action toxique
revelee par une discrete congestion, cedeme et surtout pycnose tres accen-
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tuee des cellules alveolaires, particulierement de celles de revetement. Quand
le Proces pycnotique decline, ces cellules augmentent de volume et de
nornbre ; c'est alors que se forment les tumeurs a leurs depens. b) L'action
toxique de Furethane sur les cellules alvenlaires donnerait origine C leur
mutation ; cette nouvelle lignee de cellules engendrerait des tumeurs pul-
monaires.
Activite cancerigene de nouvelles benzacridines angulaires
F. ZAJDELA et N. P. BUU-HO I (Paris).
En continuation de nos recherches sur les relations entre constitution
chirnique et activite cancerigene des derives hetero-cycliques azotes, nous
avons examine les proprietes d'une vingtaine de composes nouveaux des
series de la 5.6-benzacridine et de la 7.8-benzacridine. Les resultats obtenus
avec une lignee de souris pen sensibles montrent que, par badigeonnages
quatre de ces corps sont actifs (par ordre de carcinogenicite decroissante :
la 2.3. 10-trimethyl- la 1.4.10-trimethyl-, la 1.6.10-trimethy 1-, et la 3-phe-
ny1-10-methyl- 7,8-benzacridine). Par injection sous-cutanee, deux corps
seulement:ont produit des sarcomes : la 2,3, 10-trimethy1-5.6-benzacridine
et la 10-n-buty1-1.2.5.6-dibenzacridine.
Bone Sarcomas Produced Experimentally in the Rabbit,
Using Compounds of Beryllium
H. A. SISSONS (Londres, Grande-Bretagne).
An account of the bone changes produced in the rabbit by the intrave-
nous injection of beryllium compounds of low solubility.
In a considerable proportion of-long-term survivors of the experiments
described, multiple malignant tumours of bone develop. The initial reac-
tion of the bone-marrow to injected beryllium is the development of scat-
tered focal granulomas. Later, this is followed by extensive fibrosis of bone-
marrow, and the tumours themselves appear to have their origin in this
osteogenic fibrous tissue.
Structurally, the tumours show remarkable similarity to human bone
sarcomas. They metastasise; particularly to lymph-nodes and lungs.
Delay of Methylcholanthrene Carcinogenesis
by 1,2 5, 6-Dibenzofluorene
WILLIAM B. WARTMAN, PHILIPPE SHUBIK, WILLARD T. HILL,
B. B. REEB, D. WARREN STANGER and BYRON RIEGEL
(Evanston and Chicago, U. S. A.).
The addition of an equal amount of 1, 2, 5, 6-dibenzofluorene to methyl-
cholanthrene caused a delay in the latent period of tumor production.
CF/1 strain mice (Carworth Farms) painted with an acetone solution of
this mixture developed tumors seven weeks later than mice painted with
methylcholanthrene alone. Similar experiments with chrysene and methyl-
cholanthrene showed no such effect. The final yield of tumors was the same
in both experimental and control groups. These results could not ibe attri-
buted to differences in the general health of the animals. These results par-
tially confirm those of Lacassagne, A., Buu-Hoi, and Rudali, G.
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Histology of Co-carcinogenesis
M. H. SALAMAN (Londres, Grande-Bretagne).
It was shown by Pullinger and by Glticksmann that epidermal hyperpla-
sia produced in mice by chemical carcinogens differs histologically from
that produced by non-carcinogenic irritants. Further, Cowdry showed
that the two types of hyperplasia differ chemically.
But Berenblum claims that carcinogens alter irreversibly only a few cells
in the epidermis : latent tumour cells ?. Apart from these (probably unde-
tectable histologically or chemically) the so-called ? precancerous hyper-
plasia ? is, they believe, an incidental accompaniment of carcinogenesis.
When mouse skin, after short treatment with chemical carcinogen, is
left for 5-10 weeks, hyperplasia subsides and the skin appears normal.
Does? any abnormality persist, other than presence of a few a latent tu-
mour cells ? ?
Benzpyrene was applied to backs of mice on 6 successive days (Group A).
38 days later, when hyperplasia had practically disappeared, croton oil was
applied to the treated areas. Previously untreated mice were also painted
croton oil (Group B). Histological differences between the groups were
observed.
Differential cell counts on epidermis (Gliicksmann's method, 1945) sho-
wed definite, statistically significant, differences between A and B. In A,
percentage of resting cells (basal cells proper) rose, soon after beginning
of croton oil treatment, to high level and remained well above normal (as
it does in epidermis treated continuously withla carcinogen). In B, resting
cell percentage, after slight initial rise, fell to normal.
It thus appears that epidermis rendered hyperplastic by short treatment
with carcinogen, though it returns to apparently normal state, has suffered
a general change which does not merely consist in presence of a few ? latent
tumour cells ?.
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AMPHITHEATRE ? 2 A), (RICHELIEU)
Vendredi matin 21 juillet 1950 (de 9 h. a 12 h.)
SECTION : CANCERS PROVOQUES
Presidents : I. BERENBLUM P. R. PEACOCK
9h. ? - 9 h. 20
9 h. I20 - 9 h. 40
9 h. 40- 10 h.
10h. -10 h. 20
10 h. 20 - 10 h. 40
10 h. 40 - 11 h.
11 h. 1? -11 h. 20
11 h. 20 - 12 h. ?
BUU-HOI N. P. ? L'intervention des forces de Van
Der Waals dans les phenomenes de cancerisation
chimique.
DAUDEL P. et DAUDEL R. ? Le probleme de la
prevision des proprietes carcinogenes des substances
chimiquec.
PULLMAN A., BERTHIER G. et PULLMAN B. ?
Les caracteristiques energetiques des hydrocarbures
cancerigenes.
BOYLAND E. ? The structure of chemical carcino-
gens.
ANDERSON W. ? The emission of visible radiation
from oxidation reaction of carcinogenic and related'z
compounds.
NEISH W. J. P. ? On the formation of benzpyrene
quinones during photoiodination of unsaturated;
substances in the presence of benzpyrene.
CALCUTT G.? Chemical carcinogens as photosensiti-
sing agents.
EKWALL P. et SETALA K.? Solvents with different
lipophilic-hydrophilic properties as carriers for car-
cinogenic hydrocarbons.
SETALA K. et EKWALL P. ? Some observations
on chemical carcinogenesis using new types of sol-
vents for the carcinogenic hydrocarbons.
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L 'intervention des forces de Van der Waals
dans les phenomenes de cancerisation chimique
NG. PH. BUU-HOI (Paris).
La possibilite de ffintervention des forces de valence secondaires du type
de Van der Waals dans la creation de processus biochimiques pouvant cons -
tituer le point de depart d'un phenomene de cancerisation, est evOquee.
L'eventualite d'une telle intervention est suggeree par la grande diversite
des agents de cancerisation chimique. Ce point de vue permet d'elargir et
de completer la theorie electronique du pouvoir cancerigene des substances
chimique s .
Le probleme de la prevision des proprietes carcinogenes
des substances chimiques
P. et R. DAUDEL (Paris).
La theorie electronique suggere que les hydrocarbures conjugues carcino-
genes contiennent une region apte a reagir par addition et riche en electrons it.
On peut appeler carcinophile tout squelette hydrocarbone fpossedant une
telle region apte a l'addition.
Cette region est generalement caracterisee par une liaison possedant un
fort indice de liaison reunissant deux atomes possedant une forte valence
libre.
La thethode des etats de spin permet sans calculs la determination des
indices de liaison et des indices de valence libre. Elle permet done de voir
tres rapidement, a simple ecriture de sa formule, si un squelette contient une
region apte a l'addition, c'est-a-dire s'il est carcinophile. Une liste de sque-
lettes carcinophiles a ete ainsi constituee.
Pour constituer une molecule carcinogene, ii suffit, en principe, de placer
sur ce squelette des substituants qui elevent la charge de la region apte
l'addition.
La theorie prevoit que le substituant dolt etre place sur un atome qui,
dans le squelette, possedait une forte valence libre, et qui ne se trouve pas
trop eloigne de la dite region.
La methode des etats de spin, fournissant sans calcul les indices de va-
lence libre indique done egalement les positions on ii y a lieu de mettre un
substituant donne pour transformer un squelette carcinophile en une subs-
tance carcinogene.
En resume, la theorie electronique permet en principe d'indiquer quels
sont les aromatiques du analogues carcinophileS et de prevoir en quelle
position, il faut placer Inn substituant :donne pour former, par exemple,
la molecule la plus carcinogene qui puisse etre obtenue avec ce squelette et ce
substituant. La methode des etats de spin rend possible ces previsions sans
exiger de calculs penibles.
Des experiences realisees apres certaines previsions ont conffime celles-ci:
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Les caracteristiques energetiques des hydrocarbures
cancerigenes
A. PULLMAN, G. BERTHIER et B. PULLMAN (Paris).
L'etude par la mecanique ondulatoire de la structure fine des hydrocar-
bures cancerigenes a permis de mettre en evidence une relation entre cer-
taffies caracteristiques electronigues de cette structure et Factivite physio-
patbologique. SeIon les resultats de cette etude le pouvoir cancerigene evo-
lue parallelement a la concentration de charges sur certaines regions de ces
molecules et en particulier sur leur region K.
En vue de completer l'etude precedente nous avons recherch?aintenant
s'il existait une relation entre les caracteristiques energeligues des meme,s
hydrocarbures et leur activite cancerigene. Ces caracteristiques energetiques
sont, tout comme les caracteristiques electroniques, bees h la presence des
electrons mobiles des liaisons multiples.
Nous distinguerons deux caracteristiques energetiques principales :
1)1 L'ener gie de resonance des hydrocarbures dans leur ?t fondamental,
traduisant leur stabilite thermodynamique. II ne paralt pas y avoir de rela-
tion ldirecte entre cette energie et le pouvoir cancerigene. Par contre, une
relation parait exister entre le pouvoir cancerigene et l'energie de resonance
residuelle des hydrocarbures apres leur engagement dans un complexe
active hypothetique avec l'element cellulaire, siege de in cancerisation.
2) Les energies d'excitation correspondant au passage de molecules de
l'etat fondamental aux divers etats excites et en particulier;au premier etat
biradicalaire. Des correlations interessantes hien que limitees peuvent etre
etablies entre ces energies, et l'activite cancerigene. La determination des
energies d'excitation est utile egalement pour l'interpretation des spectres
d'absorption et de fluorescence des carbures cancerigenes.
The Structure of Chemical Carcinogens
E. BOYLAND (Londres, Grande-Bretagne).
Carcinogens contain chemically reactive groups which can be called g Car-
cinogenophores D Carcinogenophores include a) the activated phenanthrene
double bond (the K-region ? of Daudel and Pullman), b) carbon atoms
with activity like that of the meso carbon atoms of anthracene, c) the stil-
bene double bond, d) the azo group, e) the nitrogen atom of certain carba-
zoles and acridines, 1) the aromatic amino group (of aminostilbenes and
amino azo compounds), g) the sulphide group in .dibenzthionaphthenes. All
these groups are capable of reacting with perbenzoic acid. Examination of
the structure of aromatic carcinogens shows that active compounds usually
contain two such carcinogenophores.
The activity of the basic carcinogenophores and the carcinogenic activity
are often increased by substituents (frequently methyl groups) which may he
considered as ?, auxocarcinogens 1..
The Emission of Visible Radiation from Oxidation
Reactions of Carcinogenic and Related Compounds
W. ANDERSON (Glasgow, Grande-Bretagne).
Previous studies showed that oxidations of certain carcinogens and rela-
ted substances were chemiluminescent. The luminescence from reactions con-
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ducted at 37? C was a low intensity emission, too weak to make photogra-
phic recording practicable. It has been possible, however, to record the ra-
diation from reactions at raised temperatures (1500C).
The experiments were extended as follows : (1) Carcinogens and related
non-carcinogens, totalling 60 substances, from the major carcinogenic
groups, were tested with at least 3 different oxidising agents; (2) The reac-
tion products from the chemiluminescent oxidations of 3 : 3-benzpyrene and
4-dimethylaminoazobenzene were compared with those so far isolated from
the corresponding in vivo reactions. The results obtained support the view
that in vivo oxidations of carcinogens may also be chemiluminescent. Many
of the carcinogens tested participated in two, three or four luminescent
reactions. All but two of them gave rise to at least one luminescent reaction.
For these two substances there is strong evidence that they are converted
in vivo to products which give positive luminescence tests. It should be em-
phasised that closely related non-carcinogens took part similarly in chemilu-
minescent reactions in vitro. The reaction products from the 3:4-benzpyrene
and 4-dimethylaminoazobenzene oxidations with hydrogen peroxide com-
pared well with those from the in vivo reactions.
The investigations demonstrate a property common to the different
groups of carcinogenic compounds and provide an experimental basis for
the concept that the proximate causal agent in chemical carcinogenesis is
energy liberated during the oxidation of the substance administered.
On the Formation of Benzpyrene Quinones During
Photo-iodination of Unsaturated Substances
in the Presence of Benzpyrene.
W. J. P. NEISH (Sheffield, Grande-Bretagne).
It has been found that 3,4-benzpyrene readily yields its quinones (iden-
tified by chromatographic behaviour and absorption spectrophotometry)
when the hydrocarbon is present in an iodine solution in petroleum ether
(at room temperature) illuminated by visible light. This solvent, even of
analytical reagent quality contains an unsaturated compound capable of
undergoing photoiodination.
Quinone formation does not take place when solutions of benzpyrene in
petroleum ether are exposed to visible light nor does it occur when the sys-
tem containing iodine is kept in the dark, in which case also little or no
iodine consumption occurs. Thus the reaction is not due to a process invol-
ving autoxidation of the unsaturated component of petroleum ether or to
photooxidation of the hydrocarbon but is dependent on the photoiodination
process. Further evidence for this is found with model systems consisting of
cyclohexene or allylchloride in n-hexane which undergo photoiodination
and bring about quinone formation when benzpyrene is present. No oxida-
tion of benzpyrene occurs when n-hexane-iodine solutions are exposed to
light. Brown & Daniels have shown that oxygen interferes with and is con-
sumed during the process of photobromination of cinnamic acid, a reaction
which is interpreted on the basis of formation of bromoperoxy cinnamic acid
free radicals and bromo peroxides. It is concluded that iodo-peroxy radicals
or iodo-peroxides are generated during the photoiodination of unsaturated
compounds at room temperature, and these, in the presence of benzpyrene,
can bring about its oxidation to quinones.
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' Chemical Carcinogens as Photosensitising Agents
G. CALCUTT (Northwood, Grande-Bretagne).
Carcinogenic polycyclic hydrocarbons are already known to be photo-
sensitising agents. Now, tests of a large number of other carcinogenic che-
micals show that these possess this same biological property. The signifi-
cance of this feature is briefly discussed and the relationship between me-
chanism of carcinogenesis is considered.
Solvents With Different Lipophilic-Hydrophilic Properties
as Carriers for Carcinogenic Hydrocarbons
, PER EKWALL and KAI SETALA (Helsingfors, Finlande).
It is possible to prepare aqueous solutions of carcinogenic hydrocarbons
with.the aid of association colloids of various types. The resulting aqueous
solutions of the carcinogens are perfectly stable and clear. The solubilized
hydrocarbon molecules are occluded within the micelles in a lipophylic envi-
ronment, apparently in the ratio of one hydrocarbon molecule to each mi-
celle. These aqueous solutions should hence not be confused with the sus-
pensions that have been previously employed.
The fluorescence of the carcinogenic hydrocarbons is much stronger in
these aqueous colloidal solutions than when they are dissolved in acetone,
benzene, etc. The solutions easily penetrate the tissues and malignant tu-
mours are readily induced with these solutions. In this process the micelles
transport the occluded carcinogen along with them. Water- and fat-soluble
co- or anticarcinogenic substances can be applied simultaneously.
Several association colloids themselves are also in non-aqueous state
ii-
table solvents for the carcinogens. Excellent characteristics are in this res-
.pect ievealed by the Carbowaxes e (polyethylene glycols). These substances
are also more or less miscible with both water and fats.
We have used these solvents in our systematic investigations of the i:ole
of the solvent in the penetration and transport of the carcinogens. The signi-
ficanee of this appears, for example, from the following. 3:4-benzpyrene dis-
solved in a purely lipophilic solvent will not enter the cells in the wall of the
glandular part of the mouse stomach,whereas this will occur readily when
the benzpyrene is introduced in solvents with appropriate lipophilic-hydro-
philic characteristics.
Another factor whose significance is being studied is the stability of the
carcinogen solutions to the hydrogen-ion concentrations prevailing in the
various biological environments. This factor seems to be of importance espe-
cially for carcinogenesis in the gastro-intestinal canal. Several of the solu-
tions of carcinogenic hydrocarbons in association colloids possess a- high
stability in this respect. The alkyl sulphonates and taurocholate solutions
may be mentioned as examples of these.
A study of these new carcinogen solutions may be expected to throw
additional light on the transport of the carcinogens within the living organism.
Some Observations on Chemical Carcinogenesis Using
New: Types of Solvents for the Carcinogenic Hydrocarbons
KAI SETALA and 'PEE EKWALL (Helsingfors, Finlande).
When water-soluble polyethylene glycols (e Carbowaxes e) and aqueous
solutions of association colloids are used as solvents for the ;carcinogenic
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hydrocarbons and applied to the mouse skin, there is neither evaporation
of the solvent nor variation in the so-called effective concentration of the
carcinogen at the skin surface. These new solvents thus are well suitable for
quantitative studies with carcinogenic hydrocarbons.
The strong fluorescence of the carcinogenic hydrocarbons in these sol-
vents facilitates the study of the penetration of the hydrocarbons into the
various tissues.
In order to elucidate the question of under what conditions and by which
routes the carcinogen enters the living organism we have also conducted
experiments in which the skin of new-born mice were painted with these
new solutions of carcinogens. We have found that the carcinogen will pene-
trate the epidermis directly even though the pilo-sebaceous apparatus are
still undeveloped and thus a penetration through the follicular openings
cannot take place.
Our studies have, for instance, revealed that the preliminary changes
(destruction of the sebaceous elements, epilation of the skin, etc.) are de-
pending ? except on the concentration of the carcinogen? also on the che-
mical characteristics of the solvents used.
The accumulation of the carcinogenic hydrocarbons (or their metabolites)
in the glandular part of the mouse stomach has not been established with
certainty previously. We have found that e. g., 3:4-benzpyrene dissolved
in the water- and fat-soluble . Carbowax 1 500 D immediately enters the
cells of all parts of the mouse stomach, i. e., the cells of the forestomach as
those of the glandular stomach, penetrating the protective mucous bar-
rier D of the latter. Furthermore, 3 :4-benzpyrene (or its metabolites) rapidly
passes through the mucous membrane of the stomach into a system, proba-
bly a lymphatic one, of fine channels in the outers layers of ?the glandular
wall. This very fine and well-developed network of channels extends conti-
nuously throughout the outer layers of the whole stomach. This mechanism
of drainage of the fluorescent material via the routes mentioned does not
seem to have been presented earlier.
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AMPHITHEATRE u4 C ? (GUIZOT)
Lundi matin 17 juillet 1950 (de 9 h. a 12 h.)
SECTION : CANCERS ET VIRUS
Presidents : J. FURTH et F. R. PASSEY
9 h. - 9 h. 20 JONES E. E. ? A comparative study of hyperplastic
nodules in mammary glands of mice with and without
the mammary tumor inciter.
9 h. 20 - 9 h. 40 DUNN T. B. ? Morphology of mammary tumors in
mice with and without the agent : possible signifi-
cance.
9 h. 40 - 10 h. DMOCHOWSK I L. ? Spontaneous tumours in some
1 low-breast-cancer strain mice and the mammary
tumour agent.
10 h. - 10 h. 20 ORR J. W. ? Methylcholanthrene - induced mam-
mary tumours in a low-breast-cancer strain of mice.
10 h. 20- 10 h. 40 DUNNING W. F., CURTIS M. R. et MADSEN M. H.
? Diethylstilbestrol-induced mammary gland and
bladder cancer in reciprocal Fl hybrids between two
inbred lines of rats.
10 h. 40 - 11 h. o PEACOCK P. R. ? The localising effect of cautery In
1 animals bearing rous sarcoma No 1.
BRYAN W. R. ? Studies on the effects in vitro of
X radiation on the biological activity of the Rous
sarcoma virus.
11 h. -11 h. 20
11 h. 20 - 12 h. . CARR J. G., KING R. J. et ROE E. M. F. ? Ultra-
violet photomicrographs of fowl tumour tissue.
CARR J. G., HARRIS R. J. C., KING R. J. et ROE
E. M. F. ? Observation by ultra-violet photomicro-
graphy of the tumour agent from the Rous fowl
sarcoma.
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A Comparative Study of Hyperplastic Nodules in Mammary
Glands of Mice with and without the Mammary
Tumor Inciter
E. ELIZABETH JONES (Wellesley, U. S. A).
Data will be presented which indicate that hyperplastic nodules are more
numerous in the mammary glands of very old female mice from certain
inbred strains without the mammary tumor inciter than has previously
been reported. The gross and microscopic structure of these nodules will be
described and comparisons made between them and the nodules found in
the high tumor C3 H strain.
Morphology of Mammary Tumors in Mice with
and Without the Agent ; Possible Significance
THELMA B. DUNN (Bethesda U. S. A.).
Large series of mammary tumors in various strains of mice with and
without the mammary tumor agent have been examined microscopically
at the National Cancer Institute. In mice with the tumor agent, nearly all
tire tumors fall within a certain range of morphologic variation, and usually
show some reproduction of an acinar pattern. In mice without the agent a
significantly greater number of adenoacanthomas, carcinosarcomas, and
other unusual forms of mammary tumor appear. Some of these more unusual
f opus of mammary tumor are described, and their histogenesis discussed.
Of particular interest is a" molluscoid" tumor reproducing various tissues of
the mammary gland in an organoid pattern. A second unusual form, which
is readily distinguishable from other mammary tumor types, is ,composed of
multiple small cysts lined by a single layer of cuboidal epithelial cells which
are regularly invested by spindle cells, apparently of stromal origin.
Judging from these various histologic patterns it would appear that
different elements of the mammary gland may participate in the neoplastic
process. The histopathologic evidence indicates that the tumor agent acts
particularly on the acini, and that tumors of a rather uniform type result'
at a relatively early age. When the agent is absent, a greater variety of mor-
phologic types are found, some probably arising from the ducts and periduc-
tile tissue, and these appear in older mice.
Spontaneous Tumours in Some Low-Breast-Cancer Strain
Mice and the Mammary Tumour Agent
L. DMOCHOWSKI (Leeds, Grande-Bretagne).
In connection with the development of spontaneous breast tumours in
two females of C57 black low-cancer strain, after six years of observation
of this strain, an experiment was carried out to ascertain whether these
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tumours possess the milk factor. The tumour tissue was frozen and desicca-
ted in vacao, and after storage was suspended in distilled water and repea-
tedly injected into C57 x Rill and C57 x a susceptible hybrid female
mice. No breast tumours have developed in any of the hybrid mice which
have lived for 20 months. Similar results have been obtained with sponta-
neous breast tumours of a Y-low-cancer strain female and of a P-low-cancer
strain femalemouse.
It is concluded that the spontaneous breast tumours of low-cancer strain
mice which have been tested do not contain the mammary tumour agent
and that other factors such as the hormonal and genetic may be responsible
for th development of these breast tumours.
Methylcholanthrene-Induced Mammary Tumours
in a Low-Breast-Cancer Strain of Mice
J. W. ORR (Birmingham, Grande-Bretagne).
It has previously been shown that mice of the Bonser IF strain are
peculiarly susceptible to the induction of Imammary carcinoma by methyl-
cholanthrene. The effect is not apparently clue to local action, as multiple
breast tumours result when the carcinogen is administered by various routes.
This strain of mice does not possess the Bittner mammary tumour agent, nor
does such an agent appear in association with the tumours.
The present communication is concerned with the duration of treatment
necessary to provoke breast tumours. Methylcholanthrene in oily solution
was applied to multiple sites in the ventral and dorsal skin as in previous
experiments at fortnightly intervals, and discontinued after 3, 4, 5, 6, 7,
8 and 9 applications. Thereafter the mice were observed until death or the
appearance of breast tumours. More than 50 per cent, of the mice in all groups
developed mammary tumours, but the latent period was longer when treat-
ment was discontinued early, averaging 10 months (after 3 applications),
6 months (4 to 6 applications), 5 months (7 applications), 4 months (8 or
9 applications).
Another group of mice received fortnightly applications of a single drop
of methylcholanthrene solution to the interscapular skin, up to 22 applica-
tions in all; the average latent period for mammary cancer was 10 -I-
monthS.
Effect is seen in both virgin and parous females. Some features in the his-
togenesis of these tumours will be briefly considered.
Diethylstilbestrol-Induced Mammary Gland
and Bladder Cancer in Reciprocal F, Hybrids between
Two Inbred Lines of Rats
W. F. DUNNING, M. R. CURTIS, and M. E. MADSEN
(Detroit, U. S. A.).
The existance of an extra-chromosomal or milk factor in the etiology of
mouse mammary cancer was demonstrated in the reciprocal F1 hybrids
betweeri mice of strains with a high and a low mammary cancer incidence.
No confirmation of the presence of such a factor in the etiology of other neo-
plasms in mice has been obtained nor has the existance of such a factor been
demonstrated in the etiology of mammary cancer in any other species.
Reciprocal Fi hybrids were obtained from crosses between rats of the
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Copenhagen line 2 331 and A X C line 9 935. Cholesterol pellets contai-
ning 4 to 6 mg. of diethylstilbestrol were implanted subcutaneously when
the rats were 3 to 4 months of age and the incidence of mammary gland and
bladder cancer was recorded.
? Data completed to date on 51 A x C by Copenhagen hybrids show that
14 or 27 per cent developed cancer of the mammary gland in an average
-of 561 days and 9 or 18 per cent developed cancer of the bladder. Among
61 hybrids from the reciprocal cross 20 or 33 per cent developed cancer
of the mammary gland in an average of 592 days and only 3 or 5 per cent
developed cancer of the bladder. The mammary cancers were mostly papil-
lary or solid type adenocarcinoma and the bladder cancers were either papil-
lary or squamous cell carcinoma. The distribution, morphology, and histo-
genesis, of these and 20 additional tumors of other organs and tissues will
be discussed.
In this experiment there is no evidence of a maternally transmitted fac..
tor in the etiology of diethystilbestrol-induced cancer of the mammary
gland. The significant difference of 12.7 X 4.1 per cent in the occurrence of
bladder cancer in the progeny of Copenhagen and A ? C females, however,
suggests the possibility of the maternal transmission by Copenhagen fe-
males of some extrachromosomal agent, possibly infectious, which may be a
factor in the etiology of diethylstilbestrol-induced cancer of the bladder.
The Localising Effect of Cautery in Animals Bearing
Rous Sarcoma No. 1.
P. R. PEACOCK (Glasgow, Grande-Bretagne).
In the course of experiments on the effect of radiation on Rous sarcoma, a
peculiar type of recurrence in areas of radiation reaction has been noted
previously. Histological studies of such secondary tumours suggested that
an inflammatory reaction of a non-specific kind might cause similar localisa-
tion. Such localisation was originally reported by Rous and Murphy at the
sites of injection of diatomaceous earth and we have also seen it at the sites
of inflammatory reactions caused, for instance, by infected wing tabs.
Birds bearing Rous tumours were therefore cauterised at sites remote from
the tumour, by means of a small electric cautery at dull red heat. Localisa-
tion occurred within 7-10 days in the scar. Cautery applied before the deve-
lopment of a tumour elsewhere in the body, has not localised the infective
agent. Birds injected intravenously-with infective extracts of the Rous sar-
coma, followed by cautery, have only shown localisation when a tumour
grew in the subcutaneous tissues at the site of the venipuncture.
Birds bearing chemically-induced tumours or grafts from such tumours
sh owed no similar localisation of secondary tumours following cautery.
Studies on the Effects hi vitro of X Radiation
on the biological Activity of the Rous Sarcoma Virus
W. RAY BRYAN (Bethesda, U. S. A.).
The relation between dose of X radiation and the surviving activity in
irradiated samples of the Rous sarcoma virus was determined in 6 experi-
ments carried out with quantitative bioassay techniques.
A correlation was obtained between the degree of " purity" of the virus
suspension and the deviation of the results from the dose-survival curve
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that would be expected on the assum?tiol that the Rous sarcoma agen
is a virus-like entity which behaves like other known viruses in response
to irradiation.
The diameter of the radiosensitive structure of unit particles of Rous
sarcoma virus is estimated from the best results of the present series of
experiments to be 46-49 mth. This estimate does not differ significantly from
that of 70 mIs reported from other laboratories on a basis of ultracentri-
fugation studies. The possible implications of these findings with respect to
internal structure of the unit particles are discussed.
Ultra-Violet Photomicrographs of Fowl Tumour Tissue
J. G. CARR, R. J. KING and E. M. F. ROE
(Londres, Grande-Bretagne).
Observation by Ultra-Violet Photomicrography
of the Tumour Agent From The Rous Fowl Sarcoma
? J. G. CARR, R. J. C. HARRIS, R. J. KING and E. M. F. ROE
(Londres, Grande-Bretagne).
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AMPHITHEATRE ? 4 C)) (GUIZOT)
Mardi matin 18 juillet 1950 (de 9 h. a 12 h.)
SECTION: CANCERS ET VIRUS
Presidents : F. DURAN REYNALS et J. ENGELBRETH-HOLM
9 h. ? - 9 h. 20 PASSEY R. D., DMOCHOWSKI L. et GLUCKSMANN
I. ? Freeze drying of mouse mammary tissues.
9 h. 20 - 9 h. 40 HIEGER I. ? On the transmission of mouse tumours
by dried tumour tissue.
9 h. 40- 10 h. ? PASCHKIS K. E., STASNEY J. et CANTAROW A. ?
Induction of malignant tumors with pure cell frac-
tions.
10 h. ? - 10 h. 20 RODEWALD W. ? Recherches au moyen de filtrats
acellulaires de tumeurs.
10 h. 20 - 10 h. 40 GOTTSCHALK R. G. ? Problems of virus detection
in tumours and antivirus therapy.
10 h. 40 - 11 h. ? GREGORY J. E. ? Virus as a cause of cancer.
11 h. ? - 11h. 20 MOORE A. E. ? The destructive effects of viruses on
transplantable mouse tumors.
11 h. 20 - 11 h. 40 BIERMAN H. R., HAMMON W. M., EDDIE B. U.,
MEYER K. F. et SHIMKIN M. B. ? The effect
of virus and bacterial infections on neoplastic di-
seases.
11 h. 40- 12 h. ? PASSEY R. D., DMOCHOWSKI L., ASTBURY
W. T., REED R. et JOHNSON P. ? Electron
microscope and high-speed centrifuge studies of the
milk factor.
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'Synopsis of discussion in section ? Freeze Drying
of Mouse Mammary Tissues ?
R. D. PASSEY, L. DMOCHOWSKI and Mrs. I. GLUCKSMANN
(Leeds, Grande-Bretagne).
Gyel and his collaborators showed that under certain conditions mouse
tumour tissue, frozen at ?79?C. and desiccated to a state of powder, could
on reconstitution initiate the same types of tumour again on inoculation
into mice. On the assumption that the cells were killed by the treatment,
these experiments formed the basis of their claim that a virus was the agent
responsible for the transition of the tumour inducing property.
It has been found that brief centrifugation of the cell suspension gives a
clear supernatant free from cells,which is at the same time inactive, leaving
a deposit which induces tumours with great regularity, thereby demonstra-
ting that the activity remains with the cellular material.
- The inference was that some cells survive the drastic treatment as indeed
has been suggested by histological examination of the sediment.
? This view has since been supported by the growth in vitro by tissue cul-
ture technique of frozen and desiccated tumour tissues. It is concluded that
Gye and his collaborators have not demonstrated the presence of a cancer
virus by their technique.
On the Transmission of Mouse Tumours
by Dried Tumour Tissue
? I. HIEGER (Londres, Grande-Bretagne).
Drs. Gye, Craigie, Mann and Begg at the Imperial Cancer Research Fund
have reported that mouse sarcoma can be transmitted by frozen and desic-
cated tumour tissue and have concluded that their results are evidence for a
virus as the causative agent in mammalian tumours if it be assumed that
freezing I and drying kills all the cells. In experiments designed to test the
findings of the Imperial Cancer Research Fund workers, Dr. Hieger, Mr. Eve-
rett and Dr. Waymouth have investigated the effect of alterations of the
time of drying on the viability of a very rapidly growing transmissible tu-
mour, namely a sarcoma induced in a mouse by the subcutaneous injection
of commercial cholesterol. The technique of freeze-drying used here was not
identical with that of Gye's but in some ways should have been rather more
effective' in promoting rapid drying.
It was found that the sarcoma will survive freezing and drying by rapid
evacuation for a certain Maximal time, but that if the drying is continued
for a longer time the tumour will no longer grow on reconstitution with
water and transplantation into mice.
At the present stage of the investigation carried out in this Institute, it
appears that Gye's results can be explained upon some such lines as" imper-
fect dehydration leaves some cells or fragments of tumour with sufficient
viability to grow in the new host ".
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Induction of Malignant Tumors with Pure Cell Fractions
K. E. PASCHKIS, J. STASNEY and A. CANTAROW
(Philadelphia, U. S. A.).
Attempts at transmitting cancerous growth with preparations free of
living cancer cells have been unsuccessful except for the special instances
of" virus induced" cancer, such as the Rous sarcoma and the Shope papil-
loma.
Most investigators who attempted to duplicate the mode of transmission
of these virus-induced tumors with other malignant growth, used filltrates
after passing the material through various filters of the Berkefeld type.
In contradistinction the experiments reported here were performed with
cell fractions, both cytoplasmic and nuclear, obtained by differential centri-
fugation of tissue homogenates, using the procedures of Claude.
The following tumors were used (a) malignant hepatomas induced in rats
by feeding 2-acetylaminofluorene (b) Walker sarcoma 258 (c) Murphy's
rat lymphosarcoma.
Cell fractions studied include (a) chromatin (b) mitochondria (e) micro-
somes. Careful microscopic examination of these fractions showed absence
of intact cells or cell debris. Tumors were observed at the site of injection
following subcutaneous injection of chromatin from the Murphy lympho-
sarcoma, and following intrahepatic injection of mitochondria from AAF-
induced rat hepatoma.
The validity of these experiments depends on the proof of absence of
Intact tumor cells from the cell fractions employed. Careful microscopic
examination of every fraction employed was carried out, and neither intact
ccIls, nor cell debris were seen, the fraction appearing " pure " by morpho-
logical criteria. Moreover if an occassional cellwould have been transplanted
inadvertently with what appeared a pure fraction, a greatly delayed growth
would be expected. The fact that in the case of the Murphy lymphosar-
coma, the tumors induced with chromatin grew as rapidly as those following
injection of massive amounts of intact cells, adds further indirect evidence
that the growth, in the case of injection of chromatin, was due to a
tumor inciter residing in this fraction.
VersuchS mit zellfreien Filtraten aus Tumoren
WILHELMINE RODEWALD (Brackwede, Allernagne).
Nicht angegangene Impftumoren beginnen zu wachsen, wenn an einer
anderen Stelle des Kiirpers Tumorzellen injiziert werden. Bei einem Zeitab-
stand von 18-28 Tagen zwischen den beiden Impfterminen entsteht haufig
nur am Orte der Erstinjektion em n Tumor. Dieser Effekt tritt auch dann
cin, wenn der bei der zweiten Impfung libertragene Tumor anderer Art ist
als der erste.
Injiziert man Tieren, die sich gegenilber einer Beimfung mit Walkercarci-
nom oder Jensensarkom als resistent erweisen, zellfreie Filtrate aus Card-
nomen entfernt von der Impfstelle, so entsteht an der Stelle, an der zuerst
cin Tumor iibertragen wurde, eine Geschwulst, die histologisch dem zuerst
libertragenen Tumormaterial entspricht.
Durch wiederholte Injektionen zellfreier Filtrate aus Ehrlich-oder Wal-
kercarcinomen konnen bei der Maus blisartige Geschwillste hervorgerufen
werden. Die Virulenz der zellfreien Filtrate wird erhOht, wenn das Tumor-
material vor dem Filtrieren auf minus 75? C eingefroren wurde. Nach einma-
liger Injektion dieser Filtrate entstehen Geschwiilste, die hailfig zu Metas-
tasenbildung neigen.
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? Problems of ,Virus Detection in Tumors
and Antivirus TherapY
RAYMOND, G. GOTTSCHALK (Dallas, U. S. A.).
The tests used for the detection of viruses in tumors are reviewed and
discussed. The filtrability of the Rous sarcoma varies with the nature of the.
filters: The chemically induced chicken sarcoma 16 cannot be transmitted
by filtered extracts or by lyophilized cells,.but it contains an antigen closely
related to a chicken tumor virus. The ascites-producing tumors induced in
the mouse by methylcholanthrene cannot be transmitted by filtered or
irradiated fluid, and an endogenous tumor agent cannot be demonstrated
by mixed grafts of embryonic tissues and cells or extracts of mouse tumors.
Certain tests, like filtration, demonstrate the viral origin of some tumors.
Other tests, like the resistance to freezing or drying, or like immunological
evidences, must be interpreted in the light of our knowledge of the biology
of normal cells.
The demonstration of the virus origin of an increasing number of tumors.
would contribute to our understanding of cancer, but would not necessarily
afford a better therapeutic approach. Antivirus therapy is generally poor.
Previous attempts of treatment of Rous sarcoma are reviewed and tests.
with antibiotics and other substances are described.
?
Virus As a Cause of Cancer
J. E. GREGORY (Pasadena U. S. A.).
- Electron microscopic findings of biologically filtered extracts of malignant
tissue will be presented with photographic studies of cell structure.
Objects having cell structure and being consistantly the same are conside-
red virus.
The virus have been found in malignant tissue out not in normal tissue or.
benign tumor.
Human and animal cancer virus appear identical:
The inhibitory effect of a B. Subtilis produced antibiotic on malignant
tissue growth will be presented.
The Destructive Effects of Viruses on Transplantable
Mouse Tumors
ALICE E. MOORE (New York, U. S. A.).
Many years ago Levaditi and his co-workers studied the ability of viruses.
to grow in transplantable and ,spontaneous animal tumors. It was discove-
red that many viruses, for example vaccinia, rabies and lymphogranuloma,
attained high titers in some transplantable tumors. Another, the virus or
avian pest, caused definite hemorrhage and necrosis. .
For the past two years we have been engaged in studying this virus-tumor
relationship. Most of our work has been done with the virus of Russian Far-,
East encephalitis and the transplantable mouse tumor Sarcoma 180. When ,
tumor-bearing animals are inoculated intraperitoneally with virus, tumor
growth takes place for a few days and then abruptly stops. Tumors removed
from three to six days after inoculation and cut into small pieces fail to -
grow when transplanted into hosts immunized against the virus. Histological.
examination of these tumors shows complete necrosis. Tumor destruction
occurs from one to four 'days before paralysis and death of the animal and is.
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independent of tumor size or route of inoculation. That the virus has a defi-
nite affinity for the tumor is shown by the high titer in this tissue before any
virus is demonstrable in the brain.
A spectrum of many different transplantable mouse tumors has now been
studied to determine the destructive effect of the virus. The growth of so-
me has definitely been inhibited whereas that of others has not been affected.
The results of infection with other neurotropic viruses and their tumor
relationship will be presented.
The Effect of Virus and Bacterial Infections
on Neoplastic Diseases
HOWARD R. BIERMAN, MICHAEL B. SHIMKIN, WILLIAM M. D.
HAMMON, BERNICE U. EDDIE and KARL F. MEYER
(San Francisco, U. S. A.).
The virus of lymphopathia venereum has been given intravenously to five
patients with metastatic neoplastic diseases. Five patients with lymphoma
or lymphatic leukemia have been observed following the intramuscular and
intracutaneous inoculation with the virus of feline agranulocytosis. Changes
in blood chemistry, hematology and clinical status were noted. A variety
of skin eruptions were noted with the cat leukopenic virus. Marked but
temporary clinical and hematologic remissions of three weeks to six months
have been observed with varicella infections in three children with acute
lymphogenous leukemia.
Marked hematologic changes leading to temporary aplasia of the marrow
have been observed with massive hemolytic staphylococcus aureus infec-
tions in acute lymphatic leukemia.
A variety of interesting observations have been made in 16 cases, but in
po case was there noted any permanent beneficial effect as regards the neo-
plastic process.
Electron Microscope and High-speed Centrifuge
Studies of the Milk Factor
R. D. PASSEY, L. DMOCHOWSKI, W. ASTBURY, R. REED
and P. JOHNSON
Extracts of any material which is known to contain the milk-factor in
appreciable quantities, such as mammary tumours, lactating mammary
tissue and milks, etc., of high-breast-cancer strain mice,after suitable treat-
ment, present particles of the:order of 240A. in large numbers. Comparably,
in the extracts of the same materials of the low-breast-cancer strain mice,
similar particles are absent, or only present in insignificant numbers.
Breast tumour inducing activity is always associated with these particles.
Centrifugation of extracts for 2 hours at 120.000 y gravity gives a clear
supernatant free of particles, which is inactive, and a deposit of particles
which retains the tumour inducing activity.
The size of the particles will be discussed.
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AMPHITHEATRE ? 4 C a (GUIZOT)
Mercredi matin 19 juillet 1950 (de 9 h. a 12 h.)
SECTION : MICROORGANISMES ET CANCER
Presidents : L. FOULDS et I. S. YUN
9 h. ? - 9 h. 20 DILLER I. C. ? Isolation of fungi from malignant
tissue.
9 h. 20 - 9 h. 40 MORI N. ? Inframycoses et cancer.
9 h. 40 - 10 h. GERLACH F. ? Un L-organisme (micromycete) en
relation avec les tumeurs malignes.
10 h. ? - 10 h. 20 NEUMANN A. N. ? L'identite des divers soi-disant
microbes du cancer.
10 h. 20 - 10 h. 40 KOCH R. ? Contribution a l'etiologie du cancer.
Organismes elementaires virdides dans le cancer.
10 h. 40 - 11 h. ? SIRTORI C. et PIZZETTI F. ? Substances canceri-
genes et cultures bacteriennes. Nouvelle direction de
recherches sur la cancerogenese.
11 h. - 11 h. 20 SIRTORI C., TALAMAZZI F. et TRUFFINI P. ?
' Action des acridines sur les cultures vegetales.
11 h. 20 - 11 h. 40 HAVAS L. J. ? Syndromes evolutifs de l'action onco.-
genique du bacterium tumefaciens chez le Pelargo-
nium zonale, y compris teratismes et polyploidie.
11 h. 40 - 12 h. ? RAFELSON M. E., WINZLER R. J. et PEARSON
H. E. ? The effect to Theiler's GDVII virus on the
metabolic activity of amino acids in mouse brain
minces.
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Isolation of Fungi from Malignant Tissues
IRENE COREY DILLER (Philadelphia, U. S. A.)
The microscopic study of a variety of mouse and human tumors by
means of special staining techniques, particularly when applied to smear
preparations, led incidentally to the observation of spores and other fungal
structures in almost every case. When tumor tissues were cultured on
Sabouraud's or Littman's ox gall medium, mycelial forms of fungi were
readily isolated from every type of mouse tumor studied, whether trans-
planted, chemically-induced, or spontaneous, and also from all types of
human neoplasm thus far investigated. Yeast-like forms were isolated from
the blood and blood-forming organs of leukemic mice (both spontaneous
and transplanted). The basic infection in all these malignant tissues appears
to be a yeast, or a yeast-like organism, but the relationships are frequently
complicated by the presence, particularly in mouse tumors, of a second
fungus which usually overgrows plate cultures at a rapid rate. Organisms
freshly isolated from tumor tissue were pathogenic to mice, and caused
death within four to five days. The tumors thus far studied include several
transplantable sarcomas of the mouse ; sarcomas induced in ,? A strain
and C3H mice; spontaneous mammary carcinomas of mice ; mouse leuke-
mias ; human mammary carcinomas ; positively diagnosed Hodgkin's
nodes, and several human sarcomas. The characteristic organisms have
lren observed in microscopic preparations of a great many other human
tumors even though they were not cultured. Antigenic studies are now
under way in the hope of elucidating the relationships between the micro-
organisms observed and the tumor tissues from which they were isolated.
Inframycoses et Cancer
NELLO MORI (Naples, Italie)
En harmonie avec son hypothese de la nature mycetique des infravirus
(1914), fondee sur la transformation en infravirus d'un Oldiomycete patho-
gene, un premier groupe d'infravirus ? ceux A phase visible et cultivable
(Micromycetes-Borrelomycetaceae) ? a eta reconnu de nature mycetique.
Ces infravirus pourraient etre nommes Inframycetes ; les maladies qu'ils
determinent Inframycoses.
Les inframycetes semblent representer un stade metagenetique de mycetes
superieurs. Cultivables in vitro ; leurs cultures difficiles dans des conditions
habituelles ? en relation vraisemblablement avec le stade biologique de
l'inframycete ? reproduisent la maladie naturelle, tout en provoquant des
lesions graves et meme la mort. La maladie naturelle semble etre deter-
minee par la forme provenant du monde exterieur.
? Recherchant le stade provenant du monde exterieur dans le foyer
initial de la pleuropneumonie exsudative des chevres, l'A. isolait (1916)
un Oldiomycete capable de reproduire la maladie naturelle.
D'autres recherches .sur le cancer humain (1917-1925) conduisirent de
meme A la culture d'un inframycete pathogene, cachectisant, mortel .pour
des animaux de laboratoire ; mais incapable de reproduire la maladie natu-
relle, la tumeur. L'A. attribuait ses resultats negatifs (outre le stade infra-
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Tnycetique du presume mycete cancerigene) au rnanque d'un reactif animal.
Touchant l'etiopathogenese, il admit (1933) que l'inframycete demure
longtemps latent ou en symbiose et qu'il assume le pouvoir pathogene par
des causes endogenes ou exogenes.
Considerant quelques resultats de la cancerogenese experimentale, l'A.
supposa aussi que l'inframycete pourrait etre un symbiote physiologique
,cellulaire, devenu parasite a la suite de la rupture, par des causes endogenes
ou exogenes, de l'equilibre d'association.
Un L-Organisme (Micromycete) en relation
avec les Tumeurs malignes ?
F. GERLACH (Santiago, Chili)
Dans chaque cas d'une tumeur maligne, presque tout l'organisme du
porteur de tumeur se montre atteint. En certains endroits de predilection,
on pent constater regulierement la presence d'un micro-organisme, qu'on
retrouve aussi bien dans les tumeurs primaires que dans les metastases.
De fortes reactions de defense se developpent dans le systeme reticulo-
endothelial. La cachexie depend de la toxicite de ce microorganisme. L'in-
j ection de culture de ce germe a des anirnaux de laboratoire ne provoque des
tumeurs malignes que dans 4 a 5 %. Le microorganisme, par lui-meme, ne
montre aucun pouvoir cancerigene. II l'obtient seulement avec le concours
des facteurs auxiliaires. L'organisme est infecte par ce germe d? pendant
la vie infra-uterine. L'infection peut continuer ensuite sous une forme latente
qui pent devenir pathogene a chaque instant. Les nouveau-nes atteints
de la toxicose ?, presentent toujours une invasion de ce germe en quantite
enonne. La transmission du microorganisme a la souris blanche produit
le menie syndrome. Dans la plupart des cas, cette infection reste latente
(microbisme latent) jusqu'a la fin naturelle de la vie. Pendant la phase pre!.
cancereuse cet organisme saprophyte se transforme en parasite pathogene.
On le trouve dans toutes les tumeurs ainsi que dans le protoplasme des cel-
lules qu'il habite (mycetocytes). Ce germe rencontre dans l'organisme sous
les conditions indiquees pendant diverses phases de la vie, ne montre aucune
difference morphologique. Leur identite est reconnue par voie serologique
(precipitation et deviation du complement). Ce microorganisme, apparte-
nant au groupe L-organisme, est nomme Micromyces universalis innatus D.
Ii montre un cycle d'evolution semblable a celui du microorganisme de la
pleuropneumonie contagieuse des bovins et de l'agalaxie des chevres et des
moutons. II n'existe aucune tumeur maligne dans laquelle le micromycete
ne soit present en grande quantite ; il est a considerer commie facteur neces-
saire au developpement des tumeurs malignes.
L 'Menthe des divers soi-disant microbes du Cancer
ALFRED N. NEUMANN (Vienne, Autriche)
Chez la plupart des formes microbiennes decrites des les premieres recher-
ches de Rappin et Doyen jusqu'au nouveau travail de Gerlach, il s'agit du
merne microbe, tres polyrnorphe, appartenant an groupe des micromycetes.
Le microbe est filtrable et vraisemblablement le virus de Rous est identique
ou apparente a ce microbe polymorphe (M. p.). Quelques inclusions des
cellules cancereuses qui furent soupconnees de nature parasitaire (les formes
de v. Leyden, J: Koch, etc...) sont egalement apparentees au M. p. Le
microbe est ubiquitaire ; il se trouve aussi dans les conditions normales.
Mais quelquefois ii acquiert des qualites cancerigenes et meme pathogenes
pour des maladies autres _que, le cancer.
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Beitrag iur Krebsatiologie.
yiru?artige Elementarorganismen beim .Krebs
RUDOLF KOCH (Halle, Allemagne)
Der Verfasser beschreibt unter Bezugnahme und unter Fortsetzung der
Arbeiten von Jos. Koch die filtrierbaren virusartigen Entwicklungsstadien,
sozusagen die Ruheform der Cellula cancrosa. Weiterhin wird ihre Morpho-
logic und Entstehung durch Sporo- und Schizogonie und ihre Bedeutung
Mr die Krebsgenese dargestellt. Die gewucherte Epithelzelle ist somit ledi-
glich Trager eines parasitaren protozooischen Organismus. Die inzwischen
von W. E. Gye durchgeffihrte zellfreie Uebertragung von tierischen Kreb-
sen, die Verfasser und Rodewald (Arztl. Forschung 1950) bestatigen konn-
ten, sowie die Forschungen F. Gerlachs, Silbers, Rappins, Nebels, Rous,
?Shopes u. a. sowie v. Brehmers 'Ether seine Siphonospora polymorpha erhal-
ten durch die mitgeteilten neuen Befunde em v011ig anderes Gesicht und
?eine grosse Bedeutung.
Bei den nun schon von mehreren Autoren gefundenen virusartigen K?r-
perchen handelt es sich, wie der Verfasser zeigt, weder um Bakterien wie
v. Brehmer u. a. annehmen, noch urn em selbstandiges onkogenes Virus fin
Sinne der heutigen Virusforschung, sondern nur um em Entwicklungssta-
dium eines holier organisierten protozooischen Organismus, von dein es eine
ganze Gruppe nailer verwandter Individuen gibt. Bezilglich der Bedin-
gungen, unter denen die virusartigen Elemente Krebs hervorrufen konnen,
'wird auf die Arbeit Die Bedingungen der Krebsentstehung ? (Deutsches
Gesundheitswesen 1950, 5. Jhg. H. 5 S. 132) verwiesen. Die lokale Disposi-
tion, die Allgemein-bezw. Altersdisposition und der spezifische Erreger
sind conditiones sine quibus non.
Substances cancerigenes et cultures bacteriennes.
Nouvelle Direction de Recherches sur la Cancerogenese
CARLO SIRTORI et F. PIZZETTI (Milan, Italie).
A partir des conceptions modernes sur la cancerogenese interpretee
initialement ? comme une enzymopathie cytoplasmatique (?t precance-
reux) et ? successivement ? comme une lesion heterochromatinique au niveau
des centres morphogenetiques du noyau (?t cancereux), les AA. ont consi-
dere in possibilite de controler les phases de la cancerogenese sur les cultures
bacteriennes.
Les bacteries peuvent etre considerees comme des cellules isolees et au
moyen de la coloration de Robinow, qui nermet de mettre en evidence le
noyau et le cytoplasme, il est possible d'otudier leurs modifications morpho-
logiques. L'addition dans les cultures bacteriennes d'une substance cance-
'rigene, pourrait determiner des modifications moruhologiques clans les bac-
teries comparables a celles ,qu'on retrouve dans les cellules tumorales
malignes (alteration du rapport : noyau cytoplasmatique ; ,hyperchromie
du noyau ; polymorphisme, etc...). Lorsque ces modifications deviennent
stables dans les cultures successives, qui cependant presentent une augmen-
tation de l'activite proliferative, on pourrait parler de ? cancerisation des
cellules bacteriennes.
II serait possible d'etudier, a travers les modifications des milieux de
culture opportunement choisis, les etapes de in cancerisation selon leur
signification biochimique et enzymatique ; 11 serait possible avec des expe-
riences sur les antagonismes competitifs, d'affronter le probleme des sub-
'stances anticancereuses ou de la ? cancerstase ?. Les AA. rapportent les pre-
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Miers resultats de l'experience qui a ete conduite sur des cultures de B. sub-
tilis avec le 2-methylcholanthrene et dibenzanthracene.
Action des acridines sur les cultures vegetales
C. SIRTORI, F. TALAMAZZI et P. TRUFFINI (Milan, Italie)
Mode d'action des substances acridiniques sur des cultures vegetales
(controle cytologique avec : Feulgen et Carmin) ; materiel d'emploi : carotte
et ? italchina a.
Syndromes evolutifs de 1 'action oncogenique du bacterium
tumefaciens chez le Pelargonium zonale,
y compris T6ratismes et Polyploidie
LASZLO J. HAVAS (Guebwiller, France)
Des Pelargoniums zonale appartenant au meme clone furent inocules
plusieurs reprises avec des doses massives de B. tumefaciens.
Au cours des dix annees qui suivirent la premiere inoculation, la trans-
formation graduelle des plantes et leur segregation en deux types'principaux,
morphologiquement et physiologiquement divergents, a pu etre observee.
L'un de ces types reproduisit les caracteristiques essentielles du type
a gigas D et devint tetraploide. Les feuilles de certaines de ces plantes epou-
serent la forme teratologique appelee ? ascidie ?.
L'autre type epousait la forme a pleureuse a et etait caracterise par l'ex-
treme longueur, l'ageotropisme et la pleslasmie de ses tiges. Ces plantes &Mnt
restees diploldes on pouvait conclure S leur mutation factorielle. Les boa-
tures des deux types reproduisirent les memes atypies.
Le type gigas ? tetraplolde a pa etre reproduit par des cultures affaibliei3.
de B. tumefaciens, par l'heteroauxine, ainsi que par la colchicine, et le type
? pleureur a par le methylcholanthrene.
L'apport d'agents specifiques paraissant superflu pour? reproduire les
atypies en question,une theorie ? hormonale ? est presentee pour les expliquer.
The Effect of Theiler 's Gdvii Virus on the Metabolic
Activity of Amino Acids in Mouse Brain Minces
MAX E. RAFELSON, RICHARD J. WINZLER
and HAROLD E. PEARSON (Los Angeles, U. S. A.).
Various amino acids such as L-arginine monohydrochloride, cysteine hy-
drochloride L-cystine, L-histidine monohydrochloride, L-lysine monohydro-
chloride, DL-ornithine, L-tryptophane, DL-thronine and DL-serine inhibit
the propagation of Theiler's virus in flask cultures of mouse brain ; DL-ala-
nine, DL-aspartic acid, L-glutamic acid, glycine, L-leucine, DL-methionine.
L-proline and DL-valine do not inhibit the virus.
Theiler's virus was propagated in minces of one day old mouse brain sus-
pended in Simms' solution containing C"-labeled glucose. After incubation
in 50 ml Erlenmeyer flasks for 24 hours at 35? C. with and without virus, the
pooled contents of several flasks were fractionated. The amino acids were
separated by partition chromatography on starch columns and the specific
radioactivities of the various amino acids were determined. It was pre-
viously demonstrated that the virus markedly stimulates the incorporation
of glucose fragments into the tissue proteins. The present study revealed
that the carbon from the labeled glucose appears in different amounts in
'various amino acids. The presence of the virus alters the process quantitatively.
? 72 ?
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AMPHITHEATRE 4 C,> (GUIZOT)
Jeudi matin 20 juillet 1950 (de 9 h. a 12 h.)
SECTION: CYTOLOGIE, HISTOLOGIE
Pres.idents : A. V. ALBERTINI et I. PERRY
9 h. ? - 9 h. 20 KOCH R. ? Sur la cyto-histologie du carcinome-
Walker du rat.
9 h. 20- 9 h. 40 RASK-NIELSEN R. et GORMSEN H. ? On sponta-
neous and induced plasma cell neoplasia in a strain,
of mice.
9 h. 40 - 10 h. GOLDFEDER A. ? Relative morphological and bio-
chemical characteristics of analogous mammary tu-
mors.
10 h. ), - 10 h. 20 RAWLINSON H. E. ? The iron content of the mouse
mammary gland as a measure of the factors affec-
ting glandular development.
10 h. 20 - 10 h. 40 LELLI G. et MAROTTA U. ? Le collagene de quel-
ques formes de tumeurs de la mamelle vu au micros-
cope electronique.
10 h. 40- 11 h. ? BESSIS M. ? Etudes au microscope electronique des
leucocytes normaux et leucemiques.
11 h. - 11 h. 20 PIACENTINI L. ? La cellule neoplasique observee au
microscope electronique.
11 h. 20- 11 h. 40 LEBLOND C. P., STOREY W. F. et BERTALANFFY
F.? Taux du renouvellement cellulaire des organes,
Comparaison avec les statistiques de cancer.
11 h. 40 - 12 h. SYLVEN B. ? On the advantage of freezing-vacuum
desydration of tissues in morphological and cyto-
chemical research.
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-Lieber
die Zyto-Histologie des Walker-Ratten-Karzinoms
RUDOLF KOCH (Halle, Allemagne)
Ein prinzipieller Unterschied zwischen dem zytologischen Bilde des Wal-
ker-Karzinoms und dem von J. Koch beschriebenen Flexner-Jobling-Kreb-
-ses der Ratte besteht nicht. Der Walkertumor ist em n echtes Karzinom and
gehOrt zweifellos in die Gruppe der tierischen Krebse, die durch eine Varie-
? tat des on J. Koch erstmalig beschriebenen protozoischen Erregers her-
vorgerufen werden. Bei anderen Epithelschmarotzern, den Coccidien, deren
Varietaten fur die verschiedensten Tierarten pathogen sind, ist uns diese
? Tatsache langst gelau fig.
On Spontaneous and Induced Plasma Cell Neoplasia
in a Strain of Mice
RAGNA RASK-NIELSEN and HARALD GORMSEN
(Copenhague, Danemark)
In a strain of mice (Stret) with an incidence of leukremia (stem cell
-leukcemia) of 1 to 2 per cent., 17 cases of plasma cell neoplasia have been
observed.
Spontaneous development of this type of neoplasia has not been reported
previously.
Ten Of the cases observed were spontaneous generalized plasma cell
?-leukazmias and one a localized plasmocytoma, occurring in addition to
49 cases of stem cell leukmmia among approximately 3200 mice.
Among a series of approximately 1300 mice, injected with large doses'
of carcinogenic hydrocarbon, one case of generalized plasma cell leukemia
? and five cases of local, induced plasmocytoma occurred in addition to
200 cases of induced stem cell leukmmia: and. 257 local induced tumours
..(chiefly spindle-cell sarcomas).
Histologically ,the plasma cells showed a degree of differentiation varying
.'within Wide limits from case to case, with even transitions from undifferen-
tiated reticulum-cell sarcoma-like patterns to highly differentiated, abso-
ylutely typical plasmocytomas. In two instances marked mast cell infiltra-
/ tion was seen in the tumour tissue.
The observations seem to support the theories on the histogenesis of
.plasma cells from reticular cells.
Relative Morphological and Biochemical Characteristics
of analogous Mammary Tumors
Anna GOLDFEDER (New York, U. .A.)
1);__ ? -_ ? A ? ?
r
Tumors arising in inbred strains of mice-aria rats have been used by the
writer for systematic research. During the course of investigations, it was
revealed that mammary tumors, diagnosed as adenocarcinomas, proved to
differ widely in their biological and physiological characteristics, as shown
by their rate of growth, metabolic activity and their radiosensitivity.
The rate of growth, as gauged by the latent period, i. e., time elapsing
between the grafting of implants and the appearance of tumors of measurable
_size, was found to be in a ratio of about 1 : 3. The metabolic rate of these
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analogous tumors, as measured by oxygen intake and aerobic glycolysis of
tumor slices in vitro (Barcroft-Warburg Manometric technique), was also.
found to be in a ratio of about 1 : 3. ?
Studies on phosphorylated intermediates concerned in the glycolysis of
these analogous mammary tumors have been carried out by the use of the
freezing technique in situ. These results will be presented.
Cytological characteristics of the analogous tumors noted during various
phases of growth in vivo and in vitro (tissue culture) by the use of various
staining techniques will be illustrated.
A correlation will be made between the histo-morphological?characteris-
tics and the metabolic patterns of the analogous tumors. The results so far
obtained indicate that the morphological characteristics alone are not a
sufficient guide where classification of tumors is concerned.
The significance of the observations made from this study in regard to
therapy of analogous mammary tumors will be emphasized.
The Iron Content of the Mouse Mammary Gland As
a Measure of the Factors Affecting Glandular Development
H. E. RAWLINSON (Edmonton, Canada)
The epithelial cells in the mammary gland of the mature female mouse
contain heavy deposits of iron except during late pregnancy and lactation.
This iron can be easily stained in whole gland mounts and the amount of it
appears to mirror to a large extent the degree of development of the terminal
knobs and alveoli of the gland. The iron content of the inguinal glands was
.determined by wet-ashing and compared to a histological grading of the-
other mammary glands of the same animal and the close agreement indi-
?cates that such an analysis could serve as a quantitative measure of glan-
dular development. Using this method it was determined that the iron
content of the mammary glands of 25-30 week old C3H females that had
raised litters was significantly greater than that of a similar group main-
tained as virgins. In the same way differences between different mouse
strains was investigated. It is concluded that such a method could be of
value in a ;sessing various carcinogenic factors that affect the development
?of the mammary gland in mice.
Le collagene de quelques formes de tumeurs de la mamelle
vu au microscope electronique
G. LELLI at U. MAROTTA (Rome, Italie)
Partant de l'idee que, dans les tumeurs, le stroma n'est point un facteur
secondaire ou accessoire, mais qu'il represente un vrai constituant de
Torganisation des tumeurs les auteurs ont examine au microscope electro-
nique de nombreuses fibrilles collagenes appartenant au stroma idans plu-
sieurs ;formes de tumeurs de la mamelle hutnaine (carcinomas, fibroade-
nomes, mastopathies fibreuses cystiques).
Rs out constamment pa demontrer la presence de cette strie transversale
caracteristique, que les recherches de Hall, Jakus et Schmitt, de Wolpers
-et de Gross et Schmitt avaient deja nits en evidence dans le collagene des
tissus normaux.
Les mesures de l'epaisseur d'un grand nombre de ces fibrilles, ainsi que de
fibrilles collagenes du derma humain, ont permis de definir leur epaisseur
anoyenne De ces mesures, il decoule que l'epaisseur Inoyenne la plus grande
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(plus de 1 000 A) est celle des fibrilles collagenes du derme, tandis que, pour
les forxnes de tumeurs envisagees, elle est apparue inferieure a 680 A et
inversement proportionnelle au degre de maturite de la forme neoplasique
meme
Actuellement des observations sont en cours tendant a la mise en evidence
de differences eventuelles dans les caracteres de la strie des fibrillessuivant
leur provenance.
Etudes au microscope electronique des leucocytes
normaux et leucomiques
1 M. BESSIS (Paris)
Les cellules normales et leucemiques ant ete examinees par les techniques.
d'etalement et de destruction sur lame (Bessis et Bricka, 1949).
Les leucocytes presentent une ultra-structure hyaloplasmique compara-
ble a celle qui a eta anterieurement decrite dans les thrombocytes : fibrilles.
radiees ou disposees en reseau, composees elles-memes de spherules de
80 milliinicrons de diametre environ (cette disposition est particulierement
nette apres fixation a l'alcool absolu). La forme des divers organites cyto-
plasmiques (rnitochondries, granulations azurophiles, neutrophiles eosino-
philes) des leucocytes normaux est decrite ; les granulations montrent des.
images de multiplication par bipartition.
L'auteur etudie ensuite diverses inclusions para-cristallines qui semblent
specifiques de certaines cellules leucemiques : corps d'Auer, batonnets des.
lymphocytes (Bessis et Bricka, 1950) ; puis les differentes sortes de granules
que l'onlvoit occasionnellement dans les cellules des leucemies, tant aigues.
que chroniques, sans que l'on puisse encore juger de leur nature ni de leur
spacificite.
La cellule neoplasique observee au microscope electronique,
LUIGI P IACENTINI (Bologne, Italie)
L'autenr expose les premiers resultats qu'il a obtenus avec le microscope
electronique dans l'etude des cellules qui proviennent des tissus affectes de
tumeurs de differente nature.
Apres une breve presentation des techniques principales d'isolement et de
preparatiOn, ii s'arrete sur les principaux aspects observes, en soulignant
les possibilites offertes par le microscope electronique dans l'etude de In.
constitution physico-chimique intime du protoplasme de la cellule neo-
plasique.
Taux du renouvellement cellulaire des organes.
Comparaison avec les statistiques de cancer
C. P., LEBLOND, W. F. STOREY and F. BERTALANFFY
(Montr?, Canada)
A la suite d'observations faites chez le rat, les organes et tissus peuvent
etre classes approximativement comme suit sur la base du pourcentage
de cellules en voie de division; epithelium de l'intestin grele et du colon,
organe lymphatiques et moelle osseuse, follicules ovariens, tubes semini-
feres, certains autres organes sexuels,epithelium gastrique,peau et poumons-
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Il est possible de demontrer que seuls les organes de cette liste presentent
plus de mitoses qu'il n'en faut pour assurer leur croissance. Tous ces organes
doivent done produire des cellules qui sont eliminees d'une facon ou d'une
autre pour compenser la surproduction de cellules.
Si l'on compare cette liste d'organes a certaines statistiques de cancer,
on note un certain parallelisme entre l'incidence des tumeurs des divers
organes d'une part et le taux de leurs mitoses d'autre part.
On the Advantage of Freezing-Vacuum Dehydration
,of Tissues in Morphological and Cytochemical Research
BENGT SYLVEN (Stockholm, ?uede)
Commonly used mordanting procedures imply a number of tissue changes
leading to erroneous and/or misleading interpretations. These changes are
referable either to chemical effects of the particular mordanting material or
to physical effects, such as shrinkage, swelling, and other distortion of cyto-
plasmic and nuclear matter or to both. These effects can largely be avoided
? by using the method of freezing-vacuum dehydration of fresh tissue samples
?acc. to the original principles by Altmann-Gersh. A remodelled large-capacity
and refrigerated all-metal apparatus has been designed suitable for high-
-vacuum dehydration at a temperature of - 49 - 510 C. The technical data
are demonstrated. The results with reference to water-soluble protein and
other cytoplasmic constituents will be reviewed, and emphasis will be made
to show the cytological and cytochemical differences between these sections
and sections previously mordanted. In research laboratories dealing with
cytological, cyto-chemical and related problems this method is considered
essential for obtaining more correct and refined data.
? 77 ?
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AMPHITHEATRE ? 4 C>> (GUIZOT)
Vendredi matin 21 juillet 1950 (de 9 h. h 12 h.)
SECTION: CYTOLOGIE, HISTOLOGIE
Presidents : P. CtRARD et V. R. KHANOLKAR
9 h. - 9 h. 20 BURDETTE W. J. ? The use of Drosophila in cancer
research.
9 h. 20 - 9 h. 40 SCHARRER B. ? Metabolism and mortality in insects
with tumors induced by nerve severance.
9 h. 40 - 10 h. BARR M. L. ? Intranuclear changes during:accelera-
ted synthesis of cytoplasmic nucleoproteins.
10 h. D -10 h. 20 TURCHINI J. et KHAU VAN KIEN L. ? De la
detection des acides nucleiques au niveau de quelques
cellules cancereuses.
10 h. 20 - 10 h. 40 MALLET L. et PINSKY-MOORE. ? Recherches par
une methode photo-chimique des acides thymo-
nucleiques.
10 h. 40 - 11 h. SIRTORI C., PIZZETTI F. et TOSI M.? Diagnostic
cytologique (methode personnelle).
11 h. D - 11 h. 20 GLASTONE S. ? Sponge biopsy. A new method in tile
diagnosis of cancer.
11 h. 20 - 11 h. 40 GRUNER 0. C. ? Concerning the early diagnosis of
cancer (a cytological method).
11 h. 40 - 12 h. GARRIGUES R. ? Cancer vegetal et cancer animal.
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The Use of Drosophila in Cancer Research
WALTER J. BURDETTE (New Orleans, U. S. A.).
The use of Drosophila as a test animal in the study of atypical growth,
presents certain advantages. Large numbers of flies may be obtained quickly
and economically. Culture conditions are more easily controlled, and large
numbers of carefully studied stocks with marker genes and chromosome
aberrations are available for experimental purposes. Salivary chromosomes
which have been mapped minutely also offer additional help. The melano-
tic nature of most of the tumors makes identification simple, and absolu-
tely pure strains may be obtained. In addition it is possible to determine
mutation rate in an objective manner.
? The following incidence of spontaneous tumors was found in 8 of 10 stocks:
studied :
tug tu' bw tu tuwPs 1z3f to 36e tu 48j tu 36a
Number 1
?
334
?
469 1
?
497
?
407
?
717
?
303
?
920
?
1 641
% with
Tumors
43.3
28.9
26.9
19.5
4.9
4.9
4.5
1.6
Genes for 1(/)7 and we sn B 1-1 are associated with a lethal effect on the lar?
vae. The tug stock has been especially studied since it has such a high inci-
dence of tumors, and through the use of inversions and appropriate crosses.
an isogenic stock has been obtained. The main genetic factor has been tr-
eed to the second chromosome since the tumors appear only when that chro?
mosome is present. There were 138 tumors among 305 flies with this chromo-
some homozygous and 1 tumor among 537 individuals heterozygous for-
second chromosome genes from this stock. Data obtained utilizing nitro-
gen mustard and 20-methylcholanthrene indicate that although some che-
micals may have both carcinogenic and mutagenic properties, this is not
always the case. The 10 lethal mutations found among 10,108 chromosomes
tested after treatment with 20-methylcholanthrene were not in excess of
that expected from control data (2 among 2,822). It has also been possible
to determine effects on tumor incidence and mutation rate simultaneously.
Metabolism and Mortality in Insects with Tumors Induced
by Nerve Severance
BERTA SCHARRER (Denver, U S. A.).
In the insect, Leucophaea maderae (Orthoptera), tumors develop after-
severance of the recurrent nerve in organs supplied by this autonoinic
nerve, i. e., in the ,anterior alimentary canal (foregut and .stomach) and in
the salivary organs (salivary reservoir and glands). Some of these tumors.
exhibit signs of malignancy. The tumor incidence is high (75-80 %). Morta-
lity shows a sex-linked difference, in that females die sooner than males. In a
representative experimental series the mean survival rate, was 56.2 days for.
tumor bearing females, 113.3 days for males. Males and females, castrated
several weeks klor. to nerve severance, did not differ in tumor mortality :
The mean survival rates in tumor bearing castrates (females, 80.1 days
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males 80.2 days) were equal and represented values intermediate between
those of non-castrate males and females. The higher susceptibility to tumors
in reproducing females seems to be related to the greater lability in their
metabolic pattern. Fat determinations in castrate and non-castrate tumor
animals, and in normal, starved, and castrate controls support this assump-
tion. The fat content of whole animals (determined in collaboration with
V. T. Wilson) differs significantly in both sexes. Tumor bearing males, with
and without gonadectomy, had low fat values, while the values in tumor.
bearing females ranged from starvation to normal and castration levels-
Thus, in at least some of the analyzed females, death cannot be attributed
to starvation due to tumorous changes in the alimentary canal, since it
occurred at a time when the fat reserves were not yet diminished.
Intranuclear Changes During Accelerated Synthesis
of Cytoplasmic Nucleoproteins
MURRAY L. BARR (London, Canada).
The nerve cell, because of its morphological characteristics, is especially
suitable ,for cytological studies of nucleoprotein metabolism.
The Nissl material of motor cells in the cat was depleted by antidromic
stimulation. The withdrawal of Nissl material reaches a maximum two to
three days following an eight hour period of stimulation. The reduction of
cytoplasmic nucleoprotein initiates a sequence of events on the part of
certain nuclear structures which appear to participate in the rapid synthesis
of Nissl material. The original amount is restored within a week following
.stimulation.
The nucleolus, in both male and female cats, enlarges and becomes va-
cuolated during the period of accelerated synthesis of Nissl material. The
size of the nucleolus and its degree of enlargement under experimental condi;
tions appears to be the same in the two sexes. The nucleolar satellite (chro-
matin nucleolus or chromocentre) also enlarges during accelerated nucleo-
protein synthesis and moves toward the nuclear membrane. The behaviour
,of the satellite suggests that it, as well as the nucleolus, participates in the
synthesis of cytoplasmic nucleoproteins. The sexes, however, are not equall?,
endowed with the material composing the nucleolar satellite or chromatin
nucleolus. This body is about one micron in diameter in female neurones but
usually below the limit of resolution, with the oil immersion objective of an
-ordinary light microscope, in male neurones.
These observations are pertinent to the general problem of the intra-
cellular etiology of cancer in view of the possible role of nucleolus-associa-
ted chromatin in carcinogenesis.
De la detection des acides nucleiques au niveau
de quelques cellules cancereuses
JEAN TURCHINI et L. KHAU VAN KIEN (Montpellier, France).
Les auteurs utilisent une nouvelle reaction coloree des sucres par la 9 phe-
nyl, 2, 3, 7 trihydroxy, 6 fluorone pour la detection des acides nucleiques
cellulaires et de leurs derives.
Apres une hydrolyse acide analogue a celle de la reaction de Feulgen, on
met en evidence le ribodesose ou le ribose des acides nucleiques ou leurs
derives plus simples par une coloration bleue ou rouge orange.
Selon le degre de l'hydrolyse et l'emploi de la ribonuclease ou des sels
biliaires on distingue les reactions nucleale, cytoplasmale et nucleotidique.
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males 80.2 days) were equal and represented values intermediate between
those of non-castrate males and females. The higher susceptibility to tumors
in reproducing females seems to be related to the greater lability in their
metabolic pattern. Fat determinations in castrate and non-castrate tumor
animals, and in normal, starved, and castrate controls support this assump-
tion. The fat content of whole animals (determined in collaboration with
V. T. Wilson) differs significantly in both sexes. Tumor bearing males, with
and without gonadectomy, had low fat values, while the values in tumor.
bearing females ranged from starvation to normal and castration levels-
Thus, in at least some of the analyzed females, death cannot be attributed
to starvation due to tumorous changes in the alimentary canal, since it
occurred at a time when the fat reserves were not yet diminished.
Intranuclear Changes During Accelerated Synthesis
of Cytoplasmic Nucleoproteins
MURRAY L. BARR (London, Canada).
The nerve cell, because of its morphological characteristics, is especially
suitable ,for cytological studies of nucleoprotein metabolism.
The Nissl material of motor cells in the cat was depleted by antidromic
stimulation. The withdrawal of Nissl material reaches a maximum two to
three days following an eight hour period of stimulation. The reduction of
cytoplasmic nucleoprotein initiates a sequence of events on the part of
certain nuclear structures which appear to participate in the rapid synthesis
of Nissl material. The original amount is restored within a week following
.stimulation.
The nucleolus, in both male and female cats, enlarges and becomes va-
cuolated during the period of accelerated synthesis of Nissl material. The
size of the nucleolus and its degree of enlargement under experimental condi;
tions appears to be the same in the two sexes. The nucleolar satellite (chro-
matin nucleolus or chromocentre) also enlarges during accelerated nucleo-
protein synthesis and moves toward the nuclear membrane. The behaviour
,of the satellite suggests that it, as well as the nucleolus, participates in the
synthesis of cytoplasmic nucleoproteins. The sexes, however, are not equall?,
endowed with the material composing the nucleolar satellite or chromatin
nucleolus. This body is about one micron in diameter in female neurones but
usually below the limit of resolution, with the oil immersion objective of an
-ordinary light microscope, in male neurones.
These observations are pertinent to the general problem of the intra-
cellular etiology of cancer in view of the possible role of nucleolus-associa-
ted chromatin in carcinogenesis.
De la detection des acides nucleiques au niveau
de quelques cellules cancereuses
JEAN TURCHINI et L. KHAU VAN KIEN (Montpellier, France).
Les auteurs utilisent une nouvelle reaction coloree des sucres par la 9 phe-
nyl, 2, 3, 7 trihydroxy, 6 fluorone pour la detection des acides nucleiques
cellulaires et de leurs derives.
Apres une hydrolyse acide analogue a celle de la reaction de Feulgen, on
met en evidence le ribodesose ou le ribose des acides nucleiques ou leurs
derives plus simples par une coloration bleue ou rouge orange.
Selon le degre de l'hydrolyse et l'emploi de la ribonuclease ou des sels
biliaires on distingue les reactions nucleale, cytoplasmale et nucleotidique.
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simple and effective method for the procurement and processing of very
small tissue particles preparatory to microscopic examination. It facilitates
the demonstration of the presence of cancerous tissue in small ulcers at an
early stage of cancer, when the disease may be successfully treated.
Concerning the Early Diagnosis of Cancer
0. CAMERON GRUNER (Montr?, Canada).
The detection of early cancer by the demonstration of distinctive (?viral)
forms of inclusion body in the circulating monocytes, was brought forward
in 1917 andagain in 1942, after further extended researches. During the past
eight years, more than 3 000 cases have been studied, of which about half
were proved cancer cases, some untreated, some showing recurrence. The
remainder constituted controls.
Four 1 distinctive features in the blood are emphasized- the most impor-
tant being the presence of these same inclusions. In addition, graphs have
been constructed according to variations in the mononuclear and neutro-
phile series of leucocytes. Ascending curves in each case speak for cancer,
descending curves exclude it. Attention is also paid to the abundance of
platelets and their pathological morphology in these cases.
This cytological method of blood-diagnosis is recommended as a routine
procedure for ascertaining whether a given:case needs further clinical study
from the point of view of cancer.
Cancer vegetal et cancer animal
R. GARRIGUES (Lyon, France).
Les tumeurs vegetales connues sous le nom de crown-gall sont dues au
Phytomonas tumefaciens ; l'inoculation de ces bacteries dans la tige d'une
plante sensible engendre tres rapidement une tumeur d'aspect maim n ; la
plante peut porter en dehors du point d'inoculation, des metastases. Dans la
masse tumorale, surtout a la peripherie, on peut observer des mitoses aty-
piques. Les anomalies observees sont diverses ; absence de formation de la
paroi nouvelle, accompagnee ou non de la fusion des noyaux-freres qui
peuventl ensuite entrer en mitose, chromosomes repartis irregulierement
le long du fuseau plus ou moins fonctionnel reconstituant un noyau-fils au
nombre dc chromosomes double du noyau originel ; ces atypies iteratives
peuvent conduire a des noyaux 0 12 n chromosomes. Enfin, par inoculation
de fragments de culture de tissus de crown-gall libres de bacteries, on oh-
tient le developpement de tumeurs analogues. La transformation de la
cellule vegetale en cellule du crown-gall ne peut etre la meme que celle
de la cellule animale en cellule eancereuse. La pseudo-mutation de la
cellule Vegetale serait une sorte de surexcitation mitotique temporaire. Or,
Gautheret a montre que certaines cultures de tissu vegetal, sous l'ation de
Iheteroauxine, peuvent prendre Faccoutumance et acquerir la capacite de
proliferer sans elle. Il en serait de meme des cellules vegetales qui, au con-
tact d'un des produits de secretion de la bacterie, entreraient en prolifera,
tion, forinant la tumeur ; perdant ulterieurement leur capacite de multipli-
cation toute croissance tumorale s'arreterait.
Les tumeurs 0 Phytomonas tumefaciens forment une premiere categorie
de tumeurs neoplasiques, qui se placent avant les neoplasies cancereuses de
l'Homme et des Animaux, neoplasies qui montrent le maximum de malignite.
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AMPHITHEATRE ? 5 D ? (L. LIARD)
Lundi matin 17 juillet 1950 (de 9 h. a 12 h.)
SECTION : CHIMIOTHERAPIE EXPLRIMMTALE
Presidents: A. BUTENANDT *et A. HADDOW
9 h. ? - 9 h. 20 GRAFF S. ? Nucleic acids in cancer.
9 h. 20- 9 h. 40 WRIGHT L., WEINTRAUB S., ARONS I., SOKO-
LOFF B. et DUTCHER R. ? Metabolite antago-
nists in cancer.
9 h. 40 - 10 h.
STOCK C. C. et BUCKLEY S. M. ? Studies on the
inhibition of sarcoma 180 in mice.
10 h. ? - 10 h. 20 BOYLAND E. et WILLIAMS-ASHMAN H. G. ? The
influence of urethanes on the enzymic activity of .
normal and malignant tissues.
10 h. 20- 10 h. 40 BURCHENAL J. H., ROBINSON E., et JOHNSTON
S. F. ? Studies on the mechanism of resistance to
the 4-amino antagonists of pteroylglutamic acid in
leukemia.
10 h. 40 - 11 h. o PATERSON E. et BOLAND J. ? Clinical trial of
trimethylolmelamine and an ethyleneimine deri-
vative in malignant disease.
11 h. o - 11 h. 20 CHAHOVITCH X. ? Glutathion dans les tumeurs
experimentales. Role des capsules surrenales.
11 h 20- 12 h. o HENDRY J. A., ROSE F. L., et WALPOLE A. L. ?
New cytotoxic agents with tumour-inhibitory acti-
vity. I. Methods and results obtained with some
methylolamides.
HENDRY J. A., HOMER R. F., ROSE F. L. et
WALPOLE A. L. ? II. Bis-epoxides and related
compounds. III. Derivatives of ethyleneimine (azi-
ridine). IV. Theoretical considerations.
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Nucleic Acids in Cancer
SAMUEL GRAFF (New York, U. S. A.).
1) The incorporation of glycine and adenine and the non-incorporation
of guanine in the nucleic acids of cancer tissues have been determined.
2) A number of analogs of guanine have been synthesized and found
to lack the carcinostatic properties peculiar to guanazolo (Kidder).
3) Inibition of cancer proliferation by guanazolo is not reflected in the
incorporation of glycine or adenine by the total nucleic acids of cancer
tissues.,
4) These experiments indicate that the carcinostatic properties of guana-
zolo do not involve competitive inhibition with guanine.
5) It is concluded that cancer is a disease of a relatively small component
of the Cell and experiments based on this assumption have been devised.
Metabolite Antagonists in Cancer
L. WRIGHT, S. WEINTRAUB, I. ARONS, B. SOKOLOFF
and R. DUTCHER (New-York et Lakeland, U. S. A.).
Assuming that cancerous cells, contrary to normal cells, are unable to
synthesize guanine from adenine, G. Kidder et 'al. submitted mice, bearers
of transplanted adenocarcinoma Eo 771 and of spontaneous mammary
cancer, to treatment withalianazolo. In the case of adenocarcinoma, treat-
ment started 6 days after ttansplantation, with a daily dose of 0.5 mg given
twice a day. They noted a complete inhibition of growth, which regained
its force as soon as the treatment was discontinued.
In otir experiments we used August Rat Carcinoma, a fast-growing turrior
which never regresses, at least in our strain. Altogether two hundred rats,
with an; average weight of 180 grams, were used for experimentation. 50 rats
were given daily injections (subcutaneous) of guanazolo, twice a day, with a
total daily dose of 40 milligrams per kilo of weight. The treatment was
started on the fifth day after inoculation when the tumor was of pinhead
size. We obtained an inhibition in 75 per cent of tumors (36 rats) with a
slow growth in the rest of the tumors. At the end of three weeks of the treat-
ment, the average size of the tumor was 2.2 cm' against 9.1 cm' in the con-
trol group (25 rats). At the end of the third week the treated rats showed
some sluggishness and loss in weight (12 per cent of original weight), with
one rat l dead. In the second series of experiments, the treatment began
when the tumors had reached the average size of 3.2 cm' (50 rats). The dose
?of guanazolo was increased to a daily total dose of 100 milligrams per kilo
of weight. After three weeks of treatment the average size of the tumor had
increased to 5.6 cme as against 9.9 cm3 in the control group. This dose, ho-
wever, produced a much stronger toxic effect on the animals. Histological
examination of the adrenal gland revealed some pathological changes in the
reticularis and fasciculata zones of the gland. The assumption of Kidder et
al. that Cancerous cells differ from normal cells by their capability to meta-
bolite guanine is not substantiated by the results of our investigation with
guanazolo at least as far as August Rat Carcinoma is concerned. The result
of clinical investigation.
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Studies on the Inhibition of Sarcoma 180 in Mice
C. CHESTER STOCK, and SONJA M. BUCKLEY
/
(New York, U. S. A.)
Inhibition of the development of Sarcoma 180 ill mice has been utilized
as a screening technique to select materials with an adverse effect upon
tumor tissue. Twenty four hours after subcutaneous implantation of Sar-
coma 180 into the axillary region of mice. intraperitoneal injections of the
chemotherapeutic agent in maximum tolerated doses are initiated and
continued twice a day for 7 days. At the end of the injection period the tu-
mors are measured in two diameters by calipers. The inhibition of the tumors
in the treated animals is based on the development of the tumors in rela-
tion to the untreated controls.
Nearly 3 000 compounds have been tested. Included have been carba-
mates, fluorenes, nitrogen mustards, ethylenimines, folic acid analogs, pu-
rines, pyrimidines, pteridines, antibiotics, and miscellaneous compounds.
Fewer than 100 compounds have shown activity at tolerated doses. Of these,
the most effective have been 2,4, 6-triethylenimino-s-triazine, 3-b is (. -chlo-
roethyl) aminomethy1-4-methoxy-methyl-5-hydroxy-6-methyl pyridine di-
hydrochloride, and a number of folic acid analogs. The results obtained in
the survey will be discussed.
The Influence of Urethanes on the Enzymic Activity
of Normal and Malignant Tissues
E. BOYLAND and H. G. WILLIAMS-ASHMAN
(Londres, Grande-Bretagne)
? The effect of the in vitro addition, and the in vivo administration, of
urethanes on tissue enzyme activities will be discussed with special refe-
rence to (a) oxidative phosphorylation processes, (b) the hexokinase reac-
tion and anaerobic glycolysis and (c) the utilisation of ammonia.
Studies on the Mechanism of Resistance to the 4-Amino-
Antagonists of Pteroylglutamic Acid in Leukemia
J.H. BURCHENAL , E. ROBINSON
and S. F. JOHNSTON (New York, U. S. A.).
There is general agreement that the remissions induced in patients with
acute leukemia by the 4-amino derivatives of pteroylglutamic acid (PGA)
are temporary, and that the disease eventually becomes resistant to this
form of therapy. An analogous situation has been demonstrated in mouse
leukemia Ak4 in which, although the survival time of the treated mice may
be more than doubled, all eventually die of the disease despite continued
therapy with the 4-amino derivatives of PGA.
It has been possible, by methods somewhat similar to those used in pro-
ducing drug fast strains of bacteria, to develop a subline of leukemia Ak4,
designated Ak4R, completely resistant to therapy with 4-amino-N40- me-
thyl-PGA. This was accomplished by several serial passages of the leukemia
thru treated mice. In this subline (Ak4R) no significant increase in survival
time could be produced by therapy with any of the 4-amino derivatives
which were chemotherapeutically effective against the sensitive strain Alf.4.
This characteristic of resistance has remained fixed despite ten passages
thru untreated animals. The mechanism of this resistance to these drugs
has been studied.
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Studies on the Inhibition of Sarcoma 180 in Mice
C. CHESTER STOCK, and SONJA M. BUCKLEY
/
(New York, U. S. A.)
Inhibition of the development of Sarcoma 180 ill mice has been utilized
as a screening technique to select materials with an adverse effect upon
tumor tissue. Twenty four hours after subcutaneous implantation of Sar-
coma 180 into the axillary region of mice. intraperitoneal injections of the
chemotherapeutic agent in maximum tolerated doses are initiated and
continued twice a day for 7 days. At the end of the injection period the tu-
mors are measured in two diameters by calipers. The inhibition of the tumors
in the treated animals is based on the development of the tumors in rela-
tion to the untreated controls.
Nearly 3 000 compounds have been tested. Included have been carba-
mates, fluorenes, nitrogen mustards, ethylenimines, folic acid analogs, pu-
rines, pyrimidines, pteridines, antibiotics, and miscellaneous compounds.
Fewer than 100 compounds have shown activity at tolerated doses. Of these,
the most effective have been 2,4, 6-triethylenimino-s-triazine, 3-b is (. -chlo-
roethyl) aminomethy1-4-methoxy-methyl-5-hydroxy-6-methyl pyridine di-
hydrochloride, and a number of folic acid analogs. The results obtained in
the survey will be discussed.
The Influence of Urethanes on the Enzymic Activity
of Normal and Malignant Tissues
E. BOYLAND and H. G. WILLIAMS-ASHMAN
(Londres, Grande-Bretagne)
? The effect of the in vitro addition, and the in vivo administration, of
urethanes on tissue enzyme activities will be discussed with special refe-
rence to (a) oxidative phosphorylation processes, (b) the hexokinase reac-
tion and anaerobic glycolysis and (c) the utilisation of ammonia.
Studies on the Mechanism of Resistance to the 4-Amino-
Antagonists of Pteroylglutamic Acid in Leukemia
J.H. BURCHENAL , E. ROBINSON
and S. F. JOHNSTON (New York, U. S. A.).
There is general agreement that the remissions induced in patients with
acute leukemia by the 4-amino derivatives of pteroylglutamic acid (PGA)
are temporary, and that the disease eventually becomes resistant to this
form of therapy. An analogous situation has been demonstrated in mouse
leukemia Ak4 in which, although the survival time of the treated mice may
be more than doubled, all eventually die of the disease despite continued
therapy with the 4-amino derivatives of PGA.
It has been possible, by methods somewhat similar to those used in pro-
ducing drug fast strains of bacteria, to develop a subline of leukemia Ak4,
designated Ak4R, completely resistant to therapy with 4-amino-N40- me-
thyl-PGA. This was accomplished by several serial passages of the leukemia
thru treated mice. In this subline (Ak4R) no significant increase in survival
time could be produced by therapy with any of the 4-amino derivatives
which were chemotherapeutically effective against the sensitive strain Alf.4.
This characteristic of resistance has remained fixed despite ten passages
thru untreated animals. The mechanism of this resistance to these drugs
has been studied.
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the Walker tumour both for inhibitory action on tumour growth and, in
many cases, for specific cytotoxic activity. While no activity is shown by
the monofunctional derivatives, compounds carrying two or more such
residues have, in general, very marked effects in these tests at comparati-
vely low dose levels. More detailed consideration is accorded to the most
promising of the many active inhibitors found, to their action on the blood,
lymphoid tissues, testis and other organs and tissues, and their effects on
tumours other than the Walker.
Comparison of the results with M. 9500,2 : 4 : 6-tris-ethyleneimino-1 :3 : 5-
triazine 12 : 4 : 6-(1-aziridy1)-s-triazinel , with those obtained with allied
derivatives of a similar high level of activity indicates that several alterna-
tive compounds are available which may be expected to produce therapeu-
tical effects in man as useful as those already achieved with M. 9500.
A representative selection of compounds of this series are being tested for
carcinogenic activity. The results of these tests will be reviewed.
Now Cytotoxic Agents with Tumour-Inhibitor Activity.
IV. Theoretical Considerations
J. A. HENDRY, F. L. ROSE and A. L. WALPOLE.
(Manchester, Grande-Bretagne).
/ The first active member of the new series was tested in the course of inves-
t tigations designed to elucidate the mode of action of urethane, but subse-
quent results with other members have led us to conclude that the new
compounds are more closely related, in terms both of chemical reactivity
and cytotoxic action, to the nitrogen mustards. To account for activity
in these several series we propose a modification of the hypothesis advanced
by Goldacre, Loveless and Ross in connection, mainly, with the latter
agents. Developing the earlier work of Elmore et al. among others, these
authors proposed crosslinkage between protein or nucleoprotein molecules,
for example of sister chromatids, as the basis of the radiomimetic action cf
the nitrogen mustards upon dividing cells. Our active polymethylolamides,
bis-epoxides and bis and tris-ethyleneimino compounds also are characteri-
sed by the presence of at least two reactive (alkylating) groups in the mole-
cule. Further consideration of our results, however, reveals that only those
polyfunctional compounds are effective which are potentially capable of
polymerisation to yield linear structures with reactive groups spaced along
their axes at distances apart which are approximate multiples of 3.7A.
This distance corresponds closely to the spacing of the purine and pyri-
midine residues in the nucleic and of the amino acids of extended polypep-
tides. We conceive of such polymers, formed perhaps within the cells, for-
ming comparatively stable multi-point attachments on or between protein
and/or nucleic acid chains, such, for example, as those associated with the
chromosomes.
It is further suggested, though as yet without any experimental support,
that the tumour inhibitory and carcinogenic polycyclic hydrocarbons,
because of their planar form and potential capacity to form conjugates
with protein components (e. g. cysteine) might bring about a similar cross
linkage effect by aggregation of the hydrocarbon residues into a linear
micelle.
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/2 hours after giving single doses of compounds to ratsIbearing seven to ten-
day-old implants of the Walker tumour. A consistent association has been
found with compoundsof the types to be described between tumour inhibi-
tory activity and the capacity to induce specific radiomimetic effects (chro-
mosome fragmentation and bridge formation) in the tumour cells and this
capacity has latterly been used as an alternative procedure for the screening
of compounds as inhibitors.
Monofunctional amine reactors have proved inactive in our tests, as have
linear bifunctional methylolamides. The first active compound of the-pre-
sent series was trimetliylolmelamine (M. 7924). Results obtained with other
methylolmelarnines and allied derivatives will be presented. Trimethylolme-
lamine itself has some activity also against a transmissible mouse leukaemia
(lymphoid), a mammary carcinoma in Strong A mice, and dog leukaemia D.
In normal animals its toxic action is mainly directed against proliferating
tissues such as the haematopoietic system, lymphoid tissues, the intestinal
epithelium and the germinal epithelium of the testis, although other changer
are seen which appear to be due to a local toxic action upon epithelial and
endothelial cells in various sites. In tests which have now been in progress
for eighteen months no evidence of carcinogenic activity has been obtained.
New Cytotoxic Agents with Tumour-Inhibitory Activity.
II. Bis-Epoxides and Related Compounds
J. A. HENDRY, R. F. HOMER, P. L. ROSE and A. L. 'WALPOLE
(Manchester, Grande-Bretagne).
A series of aliphatic, alicyclic and aromatic derivatives carrying one,
two, or three ethylene oxide residues has been examined against the Walker
tumour for growth inhibitory activity and in many cases for specific cyto-
toxic action. Activity is limited to bis-functional derivatives most of which
have been of the types :
/0\
/0\ /0\ /,CH ? CH2
CH2?CH ? R? GH?CF12 or R? N
\CH? CH2
\o/
Although many of these compounds are active doses very near to the lethal
have, in general, to be given to produce marked effects.
Especial interest attaches to 1-vinyl- LI 3 : 4-cyclohexene dioxide
(M. 8840), sinCe, as well as being active in the above tests, this substance
has proved to be carcinogenic. Applied to the skin of mice it has given rise
both to carcinomas at the site of application and sarcomas in the subjacent
tissues. Vinyl-cyclohexene itself and the two mono-epoxides derived there-
from are inactive against the Walker tumour.
No tumours' have so far been obtained with the active inhibitor buta-
diene dioxide,' but this substance has given some evidence of mutagenic
activity in tests with fungal spores.
New Cytotoxic Agents with Tumour-Inhibitory Activity.
III. Derivatives of Ethyleneimine (Aziridine)
J. A. HENDRY, R. F. HOMER, F. L. ROSE and A. L. WALPOLE
(Manchester, Grande-Bretagne).
A series of aliphatic, aromatic and heterocyclic structures carrying one,
two, or more than two ethyleneimine residues has been examined against
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AMPHITHEATRE ? 5 D ? (L. LIARD)
Mardi matin 18 juillet 1950 (de 9 h. a 12 h.)
SECTION : CHIMIOTHERAPIE EXPERIMENTALL
Presidents : E. BOY LAND et M. J. SHEAR
9 h. ? - 9 h. 20 GREEN H. N. ? Shock and neoplasia.
9 h. 20 - 9 h. 40 HADDOW A. et TIMMIS G. M. ? Bifunctional sul-
phonic acid esters with radiomimetic activity.
9 h. 40- 10 h. BUTLER J. A. V. ? The action of nucleotoxic sub-
stances on nucleic acid and their nature.
10 h. ? - 10 h. 20 SMITH K. A. ? The degradation of deoxypentose
nucleic acid with radiomimetic chemicals.
10 h. 20- 10 h. 40 FLEMING R., WALTERS C. L. et WILLIAMS J. L.
? The effect of adrenal and urinary extracts on
malignant tissue.
10 h. 40 - 11 h. ? TEIR H. ? Remarkable mitotic activity following
parenteral application of tissue extract.
11 h. ? - 11 h. 20 STOCK C. C., SUGIURA K., DOBRINER K. et
RHOADS C. P. ? Studies of compounds for inhib
tion in a spectrum of tumors.
11 h. 20 - 11 h. 40 WATERMAN N. ? Considerations et experiences con-
cernant la chimiotherapie des tumeurs.
DOBROVOLSKAIA-ZAVADSKA IA N. ? Le role de
l'organisme dans la therapie des cancers.
11 h. 40 - 12 h. N
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Shock and Neoplasia
H. N. GREEN (Sheffield, Grande-Bretagne).
It was observed that the repeated induction of the shock state by hind-
limb ischaemia or by adenosine triphosphate did not significantly affect
-the , take ' or subsequent growth of a sarcoma transplant in the rat. Mito-
sis in the skin, and probably many tissues of the mouse, is immediately
suppressed in the very early stages of the shock state. The injection of
corticotrophin has a precisely similar effect. Cancer cells are relatively in-
susceptible to the anti-mitotic effect of any of these agents. Possible impli-
cations of these findings, with particular reference to tumour carbohydrate
metabolism, will be discussed.
Bifunctional Sulphonic Acid Esters
with Radiomirnetic Activity
A'. HADDOW and G. M. TIMMIS (Londres, Grande-Bretagne).
Since I it was thought probable that the radiomimetic properties of the
nitrogen mustard type of drug (I) depended, at least in part, upon the
chemical reactivity characteristic of the alkyl chloride moiety, ester groups
of appropriate chemical properties were sought which could be substituted
for the chlorine atoms. Since such ester groups would confer opportunities
for increasing the variety of chemical structures it was thus hoped to im-
prove upon the pharmacological properties of the nitrogen mustards. Inde-
pendently a correlation between chemical and biological activity in the
nitrogen mustard series has in fact been demonstrated (Haddow, Kon and
Ross, Nature 1948, 162, 824).
Appropriate esters of sulphonic, phosphoric and sulphuric acids have
been made and tested, but only the sulphonic esters have revealed activity.
The biological results are discussed.
CH2 CH2 Cl
R? N/
\
CF-LCH2C1
The Action of Nucleotoxic Substances on Nucleic Acid
and Their Nature
J. A. V. BUTLER (Londres, Grande-Bretagne).
Nitrogen and sulphur mustards produce a degradation of deoxyribo-
nucleic acid (thymus) which is similar to that produced by ionising radia-
tions. Similar effects are also produced by the free radical OH, produced
chemically and by ultra-violet irradiation of peroxides. This degradation is
demonstrated by (1) a loss of both the structural and the intrinsic viscosity
of the nucleic acid solutions (2) a decrease of molecular weight of the same
order as that produced by X-rays.
The close similarity of the actions of free radicals and the mustards sug-
gests that the reaction products of the latter with water can exist in radical
or biradiCal forms. This is possible if the central N or S atom loses one elec-
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t ron from a lone pair to the carbonium ion. The ease with which this electron
transfer occurs will be determined by the binding energies of the electrons,
as modified by the substituents. On? this view nucleotoxic properties
would not belong solely to the two-armed mustards, if the energy relations
were otherwise suitable. Other types of compounds with nucleotoxic pro-
perties (e. g. carcinogenic hydrocarbons, epoxides, stilbenes, azodyes) can
also occur in hi-radical forms, especially when suitably activated and it is
suggested that the possible occurence of such forms is a link between the
,different types of carcinogens and nucleotoxic substances.
The Degradation of Deoxypentose Nucleic Acid
with Radiomimetic Chemicals
K. A. SMITH (Londres, Grande-Bretagne).
Highly polymerised deoxypentose nucleic acid (D. N. A.) prepared from
calf thymus is degraded by di (2 chloroethyl) methylamine, a nitrogen mus-
tard, and di (2 chloroethyl) sulphide, mustard gas. The products of this
reaction have been compared with those resulting from the degradation of
D. N. A. caused by X-Rays and OH radicals.
Nitrogen mustard reacts with D. N. A. in aqueous solution in the pre-
sence of sodium bicarbonate (or other suitable buffers). A loss of viscosity
results and by dialysis through a cellophane membrane low molecular
weight substances may be separated from the reaction mixture. The small
units passing through the membrane are found to contain deoxypentose
and organically-bound phosphorus and give an ultra-violet absorption spec-
trum similar to nucleic acid with a maximum in the region of 2 600 A. Inor-
ganic phosphorus is not liberated during the reaction.
The reaction products not capable of passing through the membrane have
been found by sedimentation and diffusion measurements to be a mixture of
substances of molecular weights considerably lower than that of original
nucleic acid. Electrometric titration of the degradation products reveals
the appearance of titratable groups over the range pH 5-8.5. These may be
secondary phosphoryl groups. All available evidence thus points to the
breakage of internucleotide bonds by reaction with the nitrogen mustard
under the conditions employed.
The Effect of Adrenal and Urinary Extracts
on Malignant Tissue
R. FLEMING, C. L. WALTERS, and J. L. WILLIAMS.
(Sunbury-on-Thames, Grande Bretagne).
Marked changes have been observed in the adrenal cortices of rats in
rats in which fibrosarcomata had been induced by the carcinogen 20-methyl-
.cholanthrene; this condition produced hyperplasia of the cortex, and the
presence of a new cellular formation was noted, involving the so-called
types A & B cells. The magnitude of the changes was dependent upon the
dosage of carcinogen employed, and it is suggested that the observed effect is
part of an Antitumorogenic ), defence mechanism by the body.
Extract of adrenals from tumour bearing mice and rabbits have been
examined for their effects upon S37 transplants. Repeated experiments
using those from mice bearing the S37 sarcoma for 2 weeks have shown
some inhibitory action, whilst those from mice bearing the slower growing.
Twort carcinoma for 2 1/2 months, have shown a marked inhibitory effect,
as have the extracts from rabbits bearing chemically induced tumours.
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An ? Antitumorogenic ? factor, as evidenced in treating the S37 tumour,
and which may be related to the present in adrenal extracts, is present in
the urine from which it can be adsorbed on to activated carbon and eluted
with N caustic soda. A relationship between this factor (H. 11) and the cell
proliferation inhibition substances of Norris and Majnarich, also from urine,
is suggested.
Studies of the effect of these factors on chemically induced tumours show
a retardation of tumour development.
Remarkable Mitotic Activity Following Parenteral
Application of Tissue Extract
HARALD TE IR (Helsingfors, Finlande).
Intraperitoneal injections of tissue extract result in a considerable mito-
tic activity. The effect is greater when the extract is made from.organs of
young animals, and injections into young animals have a greater effect
than those into old animals. The effect seems to be organ specific. Fairly
large individual variations occur. Mitotic activity can be produced by
means of very small doses, often corresponding to 0.1 to 0.2 mg. of tissue
Unlike colchicine-induced mitoses "real" mitoses occur leading to an increase
in the number of cells and apparently also in the size of the cells. This acti-
vity suggests the presence of local organ specific growth factors.
Studies of Compounds for Inhibition in a Spectrum
of Tumors
C. CHESTER STOCK, KANEMATSU SUGIURA, KONRAD DOBRINER,
1 and C. P. RHOADS (New York, U. S. A.).
A spectrum of mouse and rat tumors has been employed to study the
ability of selected compounds to inhibit the development of different types
of experimental tumors in vivo. The compounds have been chosen for theore-
tical reasons or because of a demonstrated activity against some tumor.
Data are presented for several nitrogen mustards and ethylenimines, a
few folie acid analogs, and 8-azaguanine. Differences in effects upon the
various tumors are revealed.
Extensive studies recently have been made on a test of steroids for anti-
tumor activity. Three of them, cortisone acetate (compound E) (11-dehy-
dro-17-hydroxycorticosterone), compound F (17-0H-corticosterone), and
compound A (dehydrocorticosterone acetate), have shown an inhibition of
lymphosarcomas in mice. The results with these steroids and approximately
20 others lagainst Sarcoma 180, mammary adenocarcinoma E0 771, Harding-
Passey melanoma, the Patterson and Mecca lymphosarcomas, and the Ridg-
way and Wagner osteogenic sarcomas in mice, and Sarcoma 39, the Flexner-
Jobling Carcinoma, and the Walker Carcino-sarcoma 256 in rats are recor-
ded. I
Considerations et experiences concernant la chimiotherapie
des tumeurs
N. WATERMAN (Amsterdam, Hollande).
Ces dernieres annees nous out fait co :maitre plusieurs substances ch
miques exereant une influence deletere sur les cellutes tumorales. Quant
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leur mode d'action on pense surtout a une action directe locale, un empoi-
sonnement mitotique local, ou (pour les flltrats bacteriens) a une espece de
phenomene de Schwartzmann local.
En admettant refficacite occasionnelle de ces essais de chimiotherapie, il
laut toutefois remarquer qu'on a trop pense A l'application pratique, sans
se rendre assez compte des bases theoriques. Celles-l?ont d'ailleurs iden-
tiques aux regles de la chirurgie et de la radiotherapie, A, savoir :
1.) Necessite d'une relation favorable entre extension de la tumeur et
moyen therapeutique ;
20) Les interventions incomnletes sont a eviter.
Pour la chitniotherapie, ii Y a encore la complication, que, en general, le
produit chimique est beaucoup plus toxique aux stades ulterieurs qu'au
debut. Comme le salut du malade est la loi supreme, il en resulte que la chi-
miotherapie n'a pas eu encore une chance serieuse.
Personnellement, je me suis occupe depuis 1947, de la podophyllotoxine.
J'ai egalement Pu observer son action deletere sur les tumeurs transplan-
tees de toutes sortes. Son effet sur les tumeurs lymphosarcomateuses est
tres marque.
Conformement aux principes que nous nous sommes poses, nous avons
etudie l'effet de la P.D.T. sur les leucoses spontanees des souris A leur debut.
Nous disposions d'une souche, dont tous les individus developpaient une
1eucose. Nous avons divise les animaux en deux lots egaux, determines au
hasard. Un groupe a ete traite avec injections de P. D. T. sous-cutanees
dose moyenne 0.2 milligramme ; l'autre recevait de l'eau physiologique.
Il y avait une difference notable entre les deux groupes quant au poids de
foie, rate, ganglions lymphatiques et sang. Ces experiences soulignent encore
une lois la necessite de faire aussi les essais de chimiotherapie au debut.
? Le role de l'organisme dans la therapie des cancers
par N. DOBROVOLSKAIA-ZAVADSKAIA.
L Individualite de reaction et la tolerance variee aux rayons sont con-
meme pour les cancers A structure histologique semblable. Experi-
mentalement, on observe des reactions differentes des tumeurs a un meme
produit examine au point de vue de son efficacite sur revolution neoplasique.
Le role du terrain se manifeste egalement par la reprise de croissance juste
a la li mite des tissus normaux apres suspension d'un traitement a effet
inhibiteur : une telle reprise a ete observee autour de la zone peniCillee
d'hyperemie massive et irreversible, ayant supprime la proliferation neo-
plasique sous l'influence de la penicilline.peu puriflee, et A la limite de la
region d'hypobiose determinee par la penicilline purifiee.
Les modifications phenotypiques du terrain ont sfirement lieu au cours
de revolution neoplasique, surtout A regard du metabolisme intermediaire.
Nous avons observe l'accumulation d'acide pyruvique, pour des cas de can-
cers varies, avec.raggravation de la maladie, et avec la fatigue au cours de
la radi otherapie. Si les douleurs dans la tumeur meme, ou ailleurs, sont ac-
compagnees par accumulation d'acide pyruvique dans l'organisme, elles
peuvent dependre d'un oademe caracteristique le long des nerfs. Les dou-
leurs de ce genre peuvent etre utilement traitees par la decarboxylation de
l'acide pyruvique A l'aide d'aneurine, et par l'activation des processus oxydo-
reducteurs dans l'organisme.
Par consequent, retat constitutionnel et somatique de l'organisme lui-
meme merite d'?e surveille de pres au cours du traitement des cancers.
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AMPHITHEATRE ? 5 D,, (L. LIARD)
Mercredi matin 19 juillet 1950 (de 9 h. a 12 h.)
SECTION: CHIMIOTHERAPIE EXPE RIMENTALE
Presidents : E. PATERSON et N. WATERMAN
9 h. ? - 9 h. 20 SCHREK R. ? The effect of X-rays, adrenal cortex
hormones and other reagents on normal and mali-
gnant lymphocytes in vitro.
9 h. 20- 9 h. 40 BARROS AZEVEDO DE S. et CANTERO A. ? Ne-
crotizing effects with crude fungi extracts in sarcome
bearing mice and experimental observations in neo-
plastic disease.
9 h. 40 - 10 h. ? PROTTI G. ? Action d'antagonisme de la levure sur
les cellules neoplasiques.
10 h. - 10 h. 20 HERVE A. et GOVAERTS J. ? Etude de l'elimina-
tion du radiophosphore dans certains etats neopla-
siques.
10 h. 20 - 10 h. 40 JENTZER A. et WENGER P. ? Repartition ana-
tomique de l'or au cours d'applications cliniques d'or
colloldal radioact if.
10 h. 40 - 11 h. ? THOMAS J. A. ? La culture massive des tissus can-
. cereux dans l'appareil a perfusion pour gros organes
ou organismes entiers.
11 h. .p - 11 h. 20 RnBERT A. F. et HAVAS L. J. ? L'action de Pablo-
tique . Penitaline sur les tumeurs colchiciniques
et sur la croissance somatique du NC.
11 h. 20 - 11 h. 40 RONDONI P. ? Recherches sur quelques poisons de
la mitose.
11 h. 40- 12 h. ? BOTELHO C. J. ? Essais de chimiotherapie anti-
' cancereuse par des solutions iodo-iodurees acides.
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The Effect of X-Rays; Adrenal Cortex Hormones
and Other Reagents on Normal and Malignant
Lymphocytes in vitro
ROBERT SCHREK (Hines, U. S. A.).
The normal cells used in this study were derived from the thymus of the
rat and rabbit and from normal human blood. The malignant lymphocytes
were obtained from a transplantable rat lymphosarcoma and from the blood
of patients with lymphatic leukemia.
The reagents tested included x-rays adrenal cortex extracts, anisotonie
solutions and various dyes. The toxicity of the reagents was studied by the
method of unstained counts and by inoculation of the tumor cell suspen-
sions into rats.
X-rays had a delayed cytocidal action on the normal lymphocytes of the
rat, rabbit, and man. Large doses of x-rays did not kill the cells of the rat
lymphosarcoma in vitro, but did prevent the growth of the cells when ino-
culated into animals. The malignant lymphocytes of some patients with
lymphatic leukemia were not affected by irradiation but the cells from other
patients were sensitive to the reagent. It seemed that x-rays k illed mature
lymphocytes but not in-mature ones.
Adrenal cortex extract, like x-rays, was deleterious to normal but not to
malignant lymphocytes of the rat.
Many dyes were strongly toxic to cells of the rabbit but not to the normal
or malignant cells of the rat.
In general the malignant lymphoeytes were more resistant to deleteiious
agents than the normal cells. Furthermore, there were greater differences
in the reactions of the normal cells of the rat and rabbit than in the reac-
tions of normal and malignant lymphocytes of the rat.
Necrotizing Effects with Crude Fungi Extracts in Sarcoma
Bearing Mice and Experimental Observations
in Neoplastic Disease
SERGIO de BARROS AZEVEDO (Rio-de-Janeiro, Bres il)
and ANTONIO CANTER() (Montr?, Canada).
Differents extraits de champignons furent administres soit par la voie
parenterale soit par la vole buccale a des Souris greffees prealablement avec
le sarcorne 37. Un premier lot de 30 souris fut traite avec le polysaccharide
de o Serratia marcescens un deuxieme lot avec un extrait aqueux ou alcoo-
lique de pollen mixte et un troisieme lot avec de la penicilline crue, de l'ex-
trait de G. Meyer et de l'extrait des champignons de Pestalozzi. Les ani-
maux furent sacrifies 8, 12, 24 heures et 15 jours apres la derniere injection ;
l'examen cytopathologique fat effectue au niveau de la tumeur greffee. La
survie des animaux greffes avec le sarcome 37 est d'environ 25 jours. Les
traitements cites plus haut la firent prolonger a 90 jours et plus. Les modifi-
cations pathologiques ressemblent beaucoup a celles obtenues avec la col-
chicine : pycnose de noyau, hemorragie et necrose. L'extrait du pollen est le
moms actif. Dans une autre serie d'experiences la tumeur a ete incubee pen-
dant 24 heures en presence de l'extrait de G. Meyer et greffee ensuite sous
la peau de 20 souris. Apres un mois toutes les souris en experience ont ete
encore exemptes de tumeur, tandis que 18 temoins presenterent toutes des.
tumeurs considerables.
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Action d 'antagonisme de la levure sur les cellules
neoplasiques
GIOCONDO PROTTI (Busto Arsizio, Italie);
?
Les cellules neoplasiques peuvent etre lysees par ?les cellules de la levure ;
cette lyse est ?per& par une substance de nature inconnue qui est presente
dans la levure.
Une levure donnee ne peut pas lyser toutes sortes de cellules neoplasiques,
et, reciproquement, toutes les levures ne peuvent pas lyser une qualite don-
n?de cellules neoplasiques.
L, levure n'a aucune action sur les cellules normales.
Ces resultats ont ete observes histologiquement.
Les coupes histologiques preparees par la methode de Feulgen montrent
que l'acide thymonucleique des noyaux neoplasiques recolore la fuchsine
d'une facon plus ou moms intense, en rapport avec les alterations histolo-
gigues Fausees par la levure.
Nous avons examine la facon de se comporter des cultures in vitro des
?cellules epitheliales neoplasiques en posant, sur les repiquages, des suspen-
sions de levure. Ces recherches aussi (plusieurs centaines) ont demontre que
la levure possede une action antagoniste et specifique sur la cellule neopla-
s ique
Les cultures sont bloquees par Faction de la levure. On n'a observe aucun
effet dans les cas oil on avait pose les suspensions de levure sur des cultures
in vitro' d'epithelium normal et de fib roblastes.
II nous semble qu'on peut deduire les conclusions suivantes :
1? Cer taines levures ont la propriete d'attaquer seulement les cellules
neoplasiques, en y causant de graves alterations;
2. Les memes souches de levures attaquent presque toujours le meme
?type de cellules neoplasiques. De ces faits, on pourrait deduire la presenCe
dans certaines levures, d'un facteur specifique pour certaines tumeurs ;
3. Les levures sont toujours sans action sur les cellules normales. Ce fait
-serait une premiere demonstration indirecte que le comportement biochi-
mique de la cellule normale n'est pas le meme que celui de la cellule neopla-
sique.
Etude de 1 'elimination du radiophosphore
dans certains etats neoplasiques
ANDRE HERVE et JEAN GO VAERTS (Liege, Belgique).
L'etude de l'elimination urinaire du P 32 injecte par vole intraveineuse
dans di-irerses affections nous permet de faire les constatations suivantes :
1. Les leucemiques eliminent en moyenne 13 % de la dose injectee en
3 jours et 20 % en 6 jours ; les polycythemiques, 22 % en 3 jours et 30 % en
jours.
2. Les malades porteurs de lymphosarcome excretent 13.5 en 3 jours et
21.5 % en 6 jours. La retention est plus marquee dans la forme generalisee.
3. Les suj et s atteints de lymphogranulomatose eliminent 31% en 3 jours et
41.7% en 6 jours.lLa retention est plus marquee dans les formes generalisees.
4. Le traitement de ces deux dernieres affections par le P32 autorise beau-
coup moms d'espoir que celui des polycythemies et des leucemies.
L'etude de Pelimination du radio-phosphore confrontee avec les resultats
cliniques semble indiquer qu'a dose therapeutique la quantite de radio-
Clement 'fixee dans les tissus neoplasiques n'est?pas suffisante pour provo-
quer une destruction complete des masses tumorales.
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Repartition anatomique de l'or au cours d'applications
cliniques d'or colloidal radioactif
ALBERT JENTZER et PIERRE WENGER (Geneve, Suisse).
A la suite des travaux de P. F. Hahn, E. L. Carothers, J. H. Muller, l'in-
jection d'or colloidal radioactif dans les cavites semble devenir une methode
de choix d'application des isotopes. En effet, l'or colloidal metallique n'est
pas solubilise par l'organisme, ce qui permet de le concentrer dans la cavite
inj ectee.
Il nous a &Le donne d'etudier la repartition de l'or colloidal dans l'orga-
nisme humain apres injection intraperitoneale d'un cas de carcinose gene-
ralisee, inoperable, avec ascite.
Cette etude a montre qu'apres 5 jours d'irradiation, le 75,6 % de l'activite
et ait bien rest& concentree dans la zone d'injection, mais le 24,4% restant
s'etait reparti assez uniformement dans l'organisme avec une intensite plus
marquee pour la rate et les reins.
Le passage dans l'organisme a dfi se faire par les voles lymphatiques, car
les autographies montrent la grande resistance des tissus h la penetration.
D'autre part, on trouve une activite marquee des ganglions de la region irra-
diee. Cette activite est particulierement intense pour les ganglions malades.
Nous pensons qu'il y aurait matiere a l'etablissement d'une methode effi-
care pour lutter contre l'essaimage des cellules cancereuses.
L'elimination urinaire (0,25 % de l'activite totale pour 24 heures) et l'au-
tographie des reins, avec la seule zone corticale impregnee d'or, per-
mettent de considerer que pratiquement tout l'or est reste dans le corps.
La proportion d'or radioactif repandue dans l'organisme peut done, suivant
les conditions operatoires, devenir dangereuses. Nous proposons de mesurer
le degre de diffusion au moyen d'une petite injection preliminaire, suivie
crun dosage sanguin 24 heures apres (test).
Comme ii etait A prevoir, la tumeur n'a pas absorbe selectivement l'or
colloidal. Ce dernier emettant un rayonnement peu penetrant, nous pensons
qu'il est indispensable de prevoir en complement apres l'action de l'or col-
un traitement radiologique ou chirurgical, du moms pour les tumeurs
ayant un certain volume.
La culture massive des tissus cancereux
dans 1 'appareil a perfusion pour eros organes
ou organismes entiers
J. ANDRE THOMAS (Paris).
Application A la culture massive des tissus cancereux, des nouvelles
m ethodes de *perfusion prolong& par l'appareil cceur-poumon artificiels
pour grands organismes.
Possibilites de ce nouveau moyen de recherche.
L 'action de l'abiotique ? Penitaline ? sur les tumeurs
colchiciniques et sur la croissance somatique du ble
A. FRANCIS REBERT et LAZZLO J. HAVAS (Guebwiller, France).
Les proprietes oncogeniques de la colchicine ayant ete mises en evidence
chez les plantes et chez les animaux (Havas 1937, 1940), nous avons etudie
sur les phenomenes de croissance et sur l'apparition des tumeurs colchici-
niques du ble, l'action de la a penitaline principe abiotique, isole par run
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de nous (Rebert 1950) du milieu metabolique du Penicilli um italicum Wehmer.
Trois series d'txperiences representant 560 individus ont permis de don-
clure a une action pet:lenient erupechante de la penitaline.sur le developpe-
ment des tumeurs colchiciniques. Les doses utiles de l'abiotique, oscillant
entre 2,5 et 5 unites par cm3 (1 unite 0,1 mg), reduisent de 50 a 75 % le
nombre des tumeurs des tiges et de 66 a 95 % celui des racines en presence
d'une concentration de 1 pour 2 mille de colchicine.
A ces doses la penitaline, tout en accelerant la production de racines
ne deprime la croissance somatique de la plante que. de 15 %; les
concentrations inferieures a une unite par ern? augmentent le coefficient de
croissance de 16 % environ.
Bien que d'apparence antagoniste ces deux proprietes rappellent celles de
diverses autres substances antiblastiques des plantes et des animaux, enre-
gistrees sur des vegetaux en notre laboratoire. La penitaline serait done
susceptible de presenter un interet dans les recherches de therapeutiques
antittimorales.
Recherches sur quelques poisons de la mitose
P. RONDONI (Milan, Italie).
On a etudie avec des collaborateurs (BERNELLUNECCO): 10 le eyana te
de sodium (CNONa), dont la fonction caryoclasique_a ete etablie par DUS-
TIN jun. On a confirme d'abord la production de nombreuses pycnoses
dans les cellules des glandes de Galeati-Lieberkiihn de l'intestin.de la souris ;
on a demontre ensuite une action empechante sur la papainase, c'est-?ire
sur un ferment active par les thiols. En effet le cyanate reagit avec le grou-
pement sulphydryle de la cysteine. On a essaye aussi l'action sur une phos-
phatase de la muqueuse intestinale ayant comma substratum l'ac.ribonu-
cleique : action differente selon le pH et la concentration du cyanate. 2? Un
compose acridinique, bien connu dans la .therapie du paludisme (atebrifi ,
italchina). Il a peut-etre en vertu de sa longue chaine laterale une puissante
action mitoclasique sur les cultures des fibroblastes de poulet in vitro, qui le
distingue des derives plus simples de l'acridine (action purement caryo-
clasique in vivo et empechant les mitoses dans les cultures des tissus).
Les alterations de la mitose se rapprochant de celles dues a la colchicine
(m. triPolaires, obridgeso, metaphases pycnotiques, etc.), ainsi que certain e
cellules avec des pseudopodes en boule (comme on en a decrit dans les cu 1-
tures de sarcome de Rous) sont demontrees par des microphotos
Essais de chimiotherapie anti-cancereuse
par des solutions iodo-iodurees acides
C. J. BOTELHO (Paris).
1
La presente chimiotherapie iodo-ioduree acide (solution d'iode, d'iodure
de sodium, de tanin, d'acide citrique, dans l'eau distillee) est inspiree des
phenornenes physicochimiques de la o Reaction de Botelho o pour le sero-
diagnostic du cancer, dont elle utilise les reactifs modifies. La o Reaction
de Botelho o consiste a precipiter electivement eh milieu acide les globulines
anormalement en exces dans le serum des cancereux (rapport serine-globu-
line inverse).
On salt que ces globulines en exceS dans le serum des cancereux sont les
homologues des albumines tumorales dont elles proviennent (LOEPER)
La parente de ces globulines tumorales avec celles precipitees electivemen t
in vitro par la