COMPARISON OF THE CONDITIONS UNDER 



WHICH ESTROGENSAND CARCINOGENIC 



HYDROCARBONS ARE TUMORIGENIC* 



I. Atypical Epithelial and Connective-tissue Growth Induced 



BY Estrogens 



atypical cellular proliferation with metaplasia or production of new growth 

 ,/\. has been elicited with estrogens in numerous instances. In the case of 

 epithelial tissues one might mention the work of Loeb^ and of Lacassagne''' * 

 in the production of mammary adenocarcinoma in certain strains of mice, and 

 that of Hofbauer/" of Allen, Hisaw and Gardner,' Del Castillo and Sammar- 

 tino,' also Korenchevsky and Hall" with the uterine mucosa. Adenomatous 

 polyps of the uterus descending into the vagina (Lipschiitz, Vargas, Jedlicky 

 and Bellolio;'*" Bellolio"), and precancerous transformation of the portio (Loeb, 

 Suntzeff and Burns;'" Suntzeff and co-workers;'^ McEuen;" Lipschiitz and co- 

 workers'"), have been induced in the mouse, rat, and guinea pig. As to con- 

 nective tissue, sarcomata of spindle-shaped type have been elicited in mice at 

 the site of injection or elsewhere and lymphosarcomata have been reported 

 in the thymus and lymphatic glands (Gardner, Smith, Strong and Allen;'* 

 Gardner;'' Burns and co-workers;" Lacassagne'"). Subserous uterine fibroids 

 also have been elicited in the guinea pig (Nelson;""" Moricard and Cauchoix;" 

 Lipschiitz and Iglesias^). The latter authors'" established the fact that extra- 

 genital subserous fibroids can be induced also by estrogens in most of the 

 abdominal organs, as stomach, intestine, spleen, pancreas, liver, kidneys, etc. 

 (Iglesias"'). Localization, incidence, and microscopical structure of these extra- 

 genital abdominal fibroids have been studied extensively by Lipschiitz and 

 his associates (Lipschiitz, Iglesias and Vargas;'" Lipschiitz and Vargas;-" Vargas 

 and Lipschiitz;'" Murillo"'). They are to be found in both sexes, but the female 

 is more susceptible than the male (work of Koref, Jedlicky, Vargas, Chaume, 

 Szabo, and others in this department; see Palma"'). Sammartino and Gandolfo- 

 Herrera"" have fully corroborated our findings. 



II. Are these Atypical Growths Real Tumors? 



One must question whether the atypical proliferations induced by estrogens 

 should be classified as neoplasms or real tumors. The answer fully depends 

 on one's definition of tumoral growth. Tumoral growth or proliferation 

 may be defined as cellular proliferation which is localized or insular; and 

 which is atypical not only as to intensity (number of mitoses) but also as to 

 cellular structure and tissue organization, that is, is metaplastic; and which 



* This work was aided by The Jane Coffin Childs Memorial I uiui lor Medical Research 

 and bv The Rockefeller Foundation. 



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