1188 RADIATION BIOLOGY 



blood-forming organs would be particularly susceptible to leukemogenic 

 irritants. Experiments performed to test this assumption have shown 

 that the leukemogenic action of small doses of methylcholanthrene, which 

 alone rarely produces leukemia, is greatly enhanced by preirradiation 

 with doses of X radiation. It is obvious that proper timing and dosage 

 are necessary to obtain such results. A similar coleukemogenic effect 

 of these two agents was also noted by Mixer and Kirschbaum (1948) 

 and a similar synergistic effect was found in inducing thymic tumors by 

 estrogenic hormones and X irradiation (Kirschbaum et at., 1949; Kirsch- 

 baum and Mixer, 1951). Agents such as cortisone, which cause involu- 

 tion of the thymus and depress lymphopoiesis, will probably lessen the 

 liability of leukemia induction by X irradiation (Kaplan, 1951). Thus 

 the reduced incidence of leukemia may be explained when pneumonia 

 or other diseases, which cause accidental involution of the thymus, are 

 prevalent in the animal colony. 



The complexities of carcinogenesis are best illustrated by those of the 

 mammary tumor of mice which has three major causes — genetic, hor- 

 monal, and viral; if powerful, either of the latter two may cause mammary 

 tumors provided the genetic factor is present (Bittner, 1946-1947). Ion- 

 izing irradiation may produce mammary tumors in an agent-free strain 

 (Lorenz et at., 1951) ; it is not likely that this is accomplished by a direct 

 mutagenic action on cells of the mammary gland. The genes are no 

 doubt ever-present modifiers of all extrinsic agents but relatively little is 

 known on genetic factors in carcinogenesis by ionizing irradiations. The 

 uniformity of response of different strains of the same species to the same 

 dose of ionizing radiations administered under comparable conditions is 

 impressive. However, not enough work has been done on this subject. 



Certain heavy metals not possessing radioactivity have proved to be 

 carcinogenic under certain experimental conditions. The first experi- 

 ments pointing this out were performed by Schinz and Uehlinger (1942). 

 Hueper (personal communication) injected powdered uranium into the 

 bone of rats, 36 per cent of which developed tumors within six months. 

 Some of these tumors originated from the periosteum, others from 

 adjacent muscle. 



MECHANISM OF CARCINOGENESIS 



Electromagnetic as well as corpuscular radiations can be considered 

 together, since no qualitative differences have been disclosed between the 

 two. The release of energy in cells by absorption of ionizing electro- 

 magnetic radiation is accompanied by liberation of secondary electrons 

 which form ions along their path. These ions may be unstable, undergo 

 chemical changes, and interact with molecules of the tissues. The greater 

 part of the ionization will occur in the water of the tissues, resulting in 



