CARCINOGENESIS BY IONIZING RADIATIONS 1173 



mechanism; in several experiments estrogens seem to be clearly 

 implicated. 



The relation of mammary tumors to irradiation has been reviewed by 

 Lorenz ct al. (1951). Acute massive whole-body roentgen irradiation of 

 mice reduced the over-all incidence of these tumors in comparison with 

 that of the controls, but the incidence of this neoplasm was high in those 

 irradiated mice which developed granulosa-cell tumors of the ovary. 

 These findings were attributed to the well-known decrease in estrogen 

 production following irradiation of the ovaries and excessive estrogen 

 production by the granulosa-cell tumors (Furth and Butterworth, 1936). 

 Lorenz ct al. (1951) exposed C3H mice for ten to fifteen months to doses 

 of y radiation of 0.044-4.4 r daily. Although the females became sterile, 

 this type of chronic exposure had no influence upon the incidence of 

 mammary tumors. 



In another series of experiments, Lorenz ct al. (1951) irradiated mature 

 LAFi mice with doses of y radiation ranging from 0.11 to 8.8 r daily 

 (8 hours) during the entire life span of the animals. LAFi mice which 

 do not carry the milk agent have a low spontaneous incidence of mam- 

 mary tumors. All experimental groups of female mice, with the excep- 

 tion of that exposed to 0.11 r daily, showed an increased incidence of 

 mammary carcinoma ranging from 4-14 per cent. Moreover, in all but 

 the 8.8-r group irradiated during the entire life span, sarcomas of the 

 mammary gland developed, the incidence ranging from 13-25 per cent. 

 Most breast tumors were associated with granulosa-cell tumors of the 

 ovary. 



In their most recent paper, Lorenz ct al. (1951) describe the effects of 

 chronic massive y irradiation on the mammary tumor incidence in the 

 milk factor-free C3Hb mice. Forty-seven per cent of the females 

 developed mammary carcinomas and sarcomas, and 88 per cent, ovarian 

 tumors. These workers exclude the possibility that direct irradiation 

 alone was responsible for the production of these tumors and postulate a 

 combination of factors such as hormonal stimulation, direct effect on the 

 mammary gland, and other unknown indirect effects of systemic origin. 

 It is noteworthy that the mammary sarcomas like the mammary carci- 

 nomas are associated with granulosa-cell tumors. Histologic evidence of 

 estrogen secretion is often lacking in hosts bearing primary tumors, but is 

 invariably present in the subpassages of such tumors in young hosts. 

 Obviously, atrophic target organs may not respond to the hormones. 



It is noteworthy that estrogen induces carcinomas in mice and fibro- 

 adenomas in rats, indicating that both epithelial and connective tissue 

 elements of the breast are under endocrine influence. This can also be 

 demonstrated by hormonal stimulation of grafted fibroadenomas. Of 

 twenty-eight rats living longer than 150 days after repeated doses of 

 cyclotron neutrons, eleven had malignant tumors of which seven were 



