846 THE CARCINOGENIC STIMULUS II 



of the debilitating effects of hypophysectomy, spontaneous mammary tumors and hy- 

 perplastic nodules may grow progressively after pituitary removal (Gardner, 1 942) , 

 although the rate of growth is often diminished and many of the nodules regress. 

 Hypophysectomy has provided palliation in metastatic breast cancer of women 

 (Luft and Olivecrona, 1955). The mechanism underlying this response should be a 

 fruitful field of investigation. Although eleven percent of spontaneous mouse 

 mammary cancers in one series regressed following hypophysectomy, host survival 

 was not prolonged (Martinez and Bittner, 1954). The influence of hypophysectomy 

 upon mouse mammary cancer has not been adequately tested in a sufficient 

 number of strains. 



(j) Influence of thy) oid secretion on genesis and growth of tumors 



Absolute hypothyroidism induces TSH-secreting pituitary tumors in inbred 

 mice (Gorbman, 1952); partial hypothyroidism results in the development of 

 thyroid tumors (Purves et al., 1951). 



Thyroidectomy inhibits the induction of hepatic tumors in rats by acetylamino- 

 fluorene (Bielschowsky and Hall, 1953); similar effects were obtained by ad- 

 ministering thioviracil (Paschkis et al., 1948). Only if rats were made hypothyroid 

 prior to the feeding of acetylaminofluorene was the induction of liver tumors 

 inhibited, suggesting interference with the initiation of carcinogenesis. Hyper- 

 thyroidism favored the induction of hepatic tumors by butter yellow (Miller and 

 Baumann, 1951). The dye was taken up more readily by the livers of hyperthyroid 

 rats ; this could have resulted from increased intake of dye in the greater amount 

 of food ingested. Since the hyperthyroid liver did not degrade the dye as readily 

 as the normal liver, more dye could accumulate. 



When a high leukemia strain of mice was made hypothyroid with a goitrogen, 

 the development of spontaneous leukemia was favored ; this effect was correlated 

 with increase in body weight resulting from lowered metabolism (Grad et al., 1955) 

 Radio-thyroidectomy, prior to treatment with methylcholanthrene remarkably 

 reduced the incidence of methylcholanthrene-induced leukemia (Ida, unpub- 

 lished). Similar effects on radiation-induced leukemogenesis have been obtained 

 by radiothyroidectomy (Nagareda and Kaplan, 1957). The results are similar to 

 those obtained following thyroidectomy on hepatic tumor development with 

 a carcinogen, acetylaminofluorene (Bielschowsky and Hall, 1953). Inhibition of 

 leukemogenesis was greater in intact than castrated males. Whether radio- 

 thyroidectomy is effective after, rather than before, carcinogen treatment has not 

 been determined to establish the influence of the procedure on metabolism of the 

 carcinogen or on tissue response. The induction of hepatic reticulosarcoma 

 (reticuloendothelioma-hepatic histocytoma) has also been prevented by hy- 

 pothyroidism (Gillman et al., 1955). 



Hyperthyroidism increases metabolic rate and decreases body weight with a 

 given caloric intake. Increased metabolic rate with consequent decrease in body 

 weight, in spite of high caloric intake, resvilts in reducing the incidence of spon- 

 taneous mammary and pulmonary tumors (Tannenbaum and Silverstone, 1949). 

 Thus, increased metabolism may produce the same effect as caloric restriction 

 upon tumorigenesis. 



