840 THE CARCINOGENIC STIMULUS II 



Transient exposure to hormonal action may make a permanent imprint on 

 tissues, determining the ukimate development of cancer. Ovariectomy does not 

 suppress mammary tumorigenesis in the susceptible gland once adequately 

 stimulated by estrogenic hormone (Loeb, 1940). The tumor-inducing hormone 

 acts much as the chemical carcinogen which induces a skin-tumor following a 

 latent period subsequent to a single skin painting. 



(/) Tumor-promoting activity of steroids other than estrogenic 



Although the development of the normal prostate gland is under androgenic 

 influence, estrogen combined with methylcholanthrene was more carcinogenic 

 for mouse prostatic tissue than methylcholanthrene alone or administered with 

 androgen (Horning, 1952). Hepatic tumors occur more frequently in male mice of 

 strains in which the spontaneous incidence is high (Andervont, 1950b); incidence 

 in males is reduced by castration, increased in females by exogenous androgen 

 (Agnew and Gardner, 1952). Hepatic tumors are induced more readily in male 

 than female rats by hepatic carcinogens (Morris and Firminger, 1956). In two 

 high-hepatoma strains of mice males with a high caloric intake induced by gold- 

 thioglucose, developed hepatomas early; in females hyperphagia did not have a 

 comparable effect (Waxier, 1953; R. A. Liebelt, 1957). Primary carcinoma of the 

 human liver has been reported to appear more often in males, although this has 

 been questioned (Davies, 1955). With minimum doses of chemical carcinogens, 

 male mice exhibited a higher incidence of cutaneous tumors than females (Leiter 

 and Shear, 1943). 



Apparently androgenic hormone is a factor in the genesis of prostatic cancer, 

 but there is no conclusive evidence that androgens j&^r j'e are carcinogenic. Cortical 

 hormone has been implicated in the genesis of mouse leukemia (Upton and Furth, 

 1954; Silberberg and Silberberg, 1955), but, aside from these reports, the effects of 

 cortical steroids appear to impede rather than promote leukemogenesis, the inci- 

 dence of spontaneous and induced leukemia (by X-rays and carcinogenic hydro- 

 carbons) being lower or the onset delayed in cortisone-treated mice (Woolley and 

 Peters, 1953; Kirschbaum and Liebelt, unpublished) 



{g) Inhibition of tumorigenesis by steroid hormones 



Hepatic tumor incidence is lower in females than in males in both man and mouse, 

 and hepatic tumorigenesis induced by liver carcinogens (Morris and Firminger, 

 1956) occurs less readily in female than in male rats. However, sex hormones ap- 

 parently do not alter susceptibility to o-aminoazotoluene in mice (Andervont and 

 Dunn, 1947). In C3H mice receiving estrogenic hormone, the hepatic tumor inci- 

 dence was decreased (Agnew and Gardner, 1952). Excessive quantities of either 

 estrogen or androgen potentiated hepatic tumorigenesis by acetylaminoflourene in 

 the rat (Cantarow et al., 1946). 



Ovarian tumorigenesis is inhibited by estrogenic hormone following either X-irradi- 

 ation or ovarian transplantation to the spleen (Gardner, 1950). Although an- 

 drogenic hormone inhibits the development of tumors in ovaries transplanted to 

 the spleens of castrated mice, similar treatment with androgen did not prevent 

 the induction of ovarian tumors by X-rays (Gardner, 1950). Endogenous testic- 



