CARCINOGENESIS BY IONIZING RADIATIONS 1167 



Oak Ridge reactor is being studied currently. When analyzed six to 

 sixteen months after exposure, it was found that doses of 128 r of X 

 radiation and equivalent doses of slow neutrons increase the leukemia 

 incidence in mice about fourfold; 512 r and an equivalent dose of slow 

 neutrons, about sixfold. A preferential effect of neutrons as found for 

 cataract induction was not evident for leukemia induction. This slow 

 neutron flux has negligible quantities of fast neutrons, but it contains 

 much 7 radiation of high energy of about 5-6 r/minute (Darden et al, 

 1951); thus an LD 50 exposure would include exposure to 400-480 r of y 

 radiation and would account for about half the biological effectiveness as 

 concerns neoplasia induction. 



Earlier, Henshaw et al. (1947) compared the effects of fast neutrons and 

 X radiation. The incidence of malignant lymphoma following exposure 

 to a single dose of y radiation was 64 and 67 per cent in groups receiving 

 single doses of 700 and 500 r and 22-32 per cent in groups exposed to 

 26-90 n of fast neutrons, as compared to 14 per cent in the controls. The 

 r-n ratio of y radiation to fast neutrons for the different effects studied 

 varied from 8:1 to 35 : 1. 



The production of reticulum cell sarcoma in a rat by administration of 

 thorotrast was described by Onufrio (1938). This tumor is not uncom- 

 mon in the rat so this report is inconclusive, as are our observations on 

 similar neoplasms in the only two mice surviving the administration of 

 large quantities of Au 198 colloid. 



ENDOCRINE ORGANS 



The induction of neoplasia in endocrine organs by ionizing radiations is 

 of unusual interest for the following reasons: In the genesis of endocrine 

 tumors the specific (direct) irradiation effect is minor. This carcino- 

 genesis is reproducible in almost all mice in the two organs thus far 

 studied extensively (ovary and pituitary). The tumor incidence is not 

 dose-dependent in acute exposures; if a threshold dose is exceeded, almost 

 all animals develop the neoplasm. This threshold dose may be very 

 small, being below 32 r in the case of ovarian tumor induction by single 

 total-body exposure (Lorenz et al, 1947; Furth, 1949) or a total of 90 r 

 by long-continued y radiation (Lorenz et al, 1947) or, in the case of 

 pituitary tumors, many thousand rep to the thyroid (300 /ic of I 131 per 

 mouse) (Gorbman, 1949). This dose may correspond to that required to 

 destroy the functional capacity of this organ. The importance of 

 hormonal imbalance in carcinogenesis has been reviewed by Gardner 

 (1948). The ovaries are much more susceptible to irradiation than the 

 thyroid gland. After sterilization of the mouse, subsequent irradiation 

 does not modify the sequence of the carcinogenic process. The radiation 

 effect can readily be counteracted or minimized by endocrine therapy; 



