CARCINOGENESIS BY IONIZING RADIATIONS 1165 



in these hyperplastic but nonmalignant myelopoietic and lympho- 

 poietic tissues. Conversely, removal of the adrenals increases suscepti- 

 bility to the induction of leukemia by X radiation (Kaplan et al., 1951). 

 Desoxycorticosterone is without effect. The inhibitory effect of cortisone 

 is still manifest when its administration is deferred until six weeks after 

 irradiation (Kaplan et al., 1951). 



There are few experiments bearing on the pathogenesis of leukemia 

 induction by ionizing irradiation. Kaplan (1949) found that, in contrast 

 to whole-body exposure, local irradiation of mice failed to increase 

 consistently the incidence of lymphoid tumors. He concluded that the 

 induction of these tumors is not solely the result of a direct action of 

 radiation upon susceptible cells or their ancestors. In C57 black mice 

 irradiation of the upper half of the body yielded leukemia in 4 per cent 

 of the mice, lower half 2 per cent, whole body irradiation 64 per cent, 

 when a total of ten treatments were given in twelve consecutive weeks. 

 However, by alternating upper and lower body exposures within 24 hours 

 many lymphoid tumors were produced (Kaplan and Brown, 1951), sug- 

 gesting again that an indirect systemic mechanism is involved in leukemo- 

 genesis. Similarly, Lorenz and Eschenbrenner (unpublished data) 

 observed the development of lymphomas in mice of strain A irradiated 

 over the entire body with the thorax shielded, but the increase over con- 

 trols was somewhat less than after total-body irradiation and exposure of 

 the thymus alone did not increase the incidence. On the other hand, 

 Kaplan (1949) found that shielding the thymic region of C57 black mice 

 did not increase the incidence of leukemia and shielding the leg had a 

 protective effect. Similarly, direct irradiation of the thymic region with 

 the rest of the body shielded did not produce leukemias (Kaplan, 1949, 

 1951). 



These observations led to the view that the induction of leukemia is by 

 some indirect mechanism. Prolonged depression of hemopoietic activity 

 may also be a factor in eliciting lymphoid tumors (Lorenz et al., 1953). 

 Kirschbaum and Mixer (1951) found that in estrogen-treated mice 

 thymic lymphosarcoma could be induced by irradiation of the entire 

 body except the thymus and concluded that the actual leukemogen, as 

 Kaplan and others believe, is a humoral substance. Whether the 

 humoral agents protecting the body from early radiation death will also 

 lessen the likelihood of leukemia development remains to be seen. 



Little attention has been given thus far to the determination of the 

 types of experimentally induced leukemias. Some radioisotopes, as 

 Au 198 colloids, are selectively deposited in macrophages and the leuke- 

 mogenic effect of such exposures remains to be studied. Aubertin (1931) 

 and Emile-Weil and Lacassagne (1925) reported an increase of myeloid 

 leukemias among radiologists but, in subsequent analyses, all types of 

 leukemias are considered together. In mice, lymphoid tumors induced 



