1170 RADIATION BIOLOGY 



ally die after irradiation by even small doses, and a sequence of changes 

 ensues, leading to the development of neoplasms. Neither the morpho- 

 genesis nor the pathogenesis of this process is well understood. Some 

 endocrine disturbance is doubtless at play, but the term "endocrine 

 imbalance" merely covers our ignorance. 



When a threshold dose is exceeded, the onset of ovarian tumors and 

 their course follow a similar pattern; increasing the dose of radiation 

 beyond the sterilization dose (Lorenz, 1950) does not shorten the incuba- 

 tion period. This is unlike the situation found with leukemia or bone 

 tumor induction by irradiation. The induced ovarian neoplasms are 

 always slow to grow, hardly interfere with the life span of the animals, 

 and seldom metastasize. These findings suggest that there is some 

 trigger mechanism causing an all-or-none response, and this is best 

 explained on the basis of hormonal derangements initiated by the deple- 

 tion of follicles of the normal ovary by irradiation (Gardner, 1950). 

 Neither the virus nor the mutation theory can adequately explain ovarian 

 tumorigenesis by irradiation. 



Lick et at. (1949) have studied the pathogenesis of ovarian tumor induc- 

 tion. They found that X radiation did not induce tumors in an irradiated 

 ovary if the animal's second ovary remained unirradiated and functional. 

 Irradiation of a single ovary induced ovarian tumors only if the second 

 ovary was extirpated. Although a second functioning ovary inhibited 

 ovarian tumor development following unilateral contact irradiation, 

 bilateral contact irradiation resulted in tumor development. Irradiated 

 ovaries implanted intramuscularly into irradiated and nonirradiated 

 groups of spayed LAFi hybrid mice gave rise to many granulosa-cell 

 tumors, luteomas, and related neoplasms (Kaplan, 1950a). No such 

 tumors occurred when irradiated ovaries were implanted into nonirradi- 

 ated, nonovariectomized mice. In concluding that intact ovarian endo- 

 crine function inhibits the development of tumors in irradiated ovarian 

 grafts, Kaplan confirmed the observations of Lick et al. (1949) and sug- 

 gested that both a direct and an indirect mechanism may be involved in 

 the induction of ovarian tumors by irradiation. 



The induction of ovarian tumors in mice by exposure to ionizing radia- 

 tions, even though it is of unusual interest, may represent a special case. 

 Thus far (fifteen years after the original observations were made), no 

 other species has been found to be susceptible to ovarian tumor induction 

 by irradiation. This carcinogenesis requires no more than a single 

 exposure, once the threshold is exceeded; it is not dose-dependent, has a 

 long tumor-development time (approximately one year), and occurs in 

 almost all exposed mice after about one and a half years. 



Sterilization of women by X radiation was practiced some years ago. 

 Whether X irradiation has increased the frequency of carcinoma in the 

 reproductive organs of women has been the subject of much debate. The 



