CARCINOGENESIS BY IONIZING RADIATIONS 1189 



the formation of OH, H, and other radicals. These radicals will interact 

 with different cellular constituents. This fundamental ionization process 

 is identical for all ionizing radiations whether electromagnetic or cor- 

 puscular. A biologic system can recover at least partially if sufficient 

 time elapses between successive ionization events. 



Concerning views and findings relative to the mode of action of radia- 

 tions on living cells, the reader is referred to Scott (1937), Lea (1947), 

 Tobias (1951) and Chap. 6 of this book, by Zirkle. 



If a single ionization event can cause a carcinogenic change by a direct 

 action of the radiation on the cell, the carcinogenic action will be inde- 

 pendent of dose rate, but a minimum dose will be required to induce a 

 macroscopic tumor during the life span of the animal. On the other 

 hand, if several ionization events are necessary for the carcinogenic 

 change, the action of the radiation may depend on the dose rate as is the 

 case with particles of low specific ionization, such as penetrating X or y 

 rays. 



A survey of the facts gathered indicates a multiplicity of mechanisms 

 by which neoplasia is produced by ionizing radiations. Instances of both 

 direct and indirect effects are evident, although they are not always 

 clearly identified. The immediate cause of the neoplastic change is, how- 

 ever, still hidden. 



In the genesis of tumors of endocrine organs, such as pituitary tumors 

 which arise following thyroid destruction by I 131 , radiation may do 

 barely more than destroy the thyroid. Similarly, an endocrine "imbal- 

 ance" brought about by ovarian irradiation appears to be the major if 

 not the sole force in the genesis of ovarian tumors. It is possible that 

 thyroid tumors arising after administration of I 131 are caused by the 

 combination of a local effect on the cells and excessive output of thyroid- 

 stimulating hormones by the pituitary. 



The "bone seekers" such as Sr 8990 , mesothorium, and radium, on the 

 contrary, seem to exert their effect directly on osteogenic cells with 

 which they come in contact. Injury and sustained regenerative efforts 

 are characteristic events in the course of evolution of both bone and skin 

 tumors. 



If it is assumed that neoplasia induction requires a new type of cell 

 with permanently altered reproduction, carcinogenesis is best looked upon 

 either as a special type of mutation or that of abnormal differentiation 

 (Waddington, 1947; Henshaw, 1945). Waddington relates the problem 

 of the origin of cancer to that of cellular variations, in particular to those 

 that are discontinuous and irreversible, but he considers carcinogenesis to 

 be of a special type. Henshaw considers mutation a plausible explana- 

 tion of neoplasia if this term is applied to irreversible changes in extra- 

 chromosomal as well as chromosomal constituents of cells. Mutation in 

 this sense, however, does not differ from differentiation (Henshaw, 1945). 



