1168 RADIATION BIOLOGY 



this is proved in the case of ovarian tumors (Li and Gardner, 1949; 

 Gardner, 1950; Kaplan, 1950a) and pituitary growths (Furth, 1951, 

 unpublished data). 



Gonads. Many studies of the early effects of radiations on the gonads 

 have been reviewed by Warren (1942-1943). It is uncertain whether 

 irradiation within the permissible dose would cause tumors of the testes 

 and whether localized massive irradiation of the testis would give rise to 

 specific tumors; on the other hand, the ovary of the mouse is highly sensi- 

 tive to neoplasia induction. 



In a series of excellent papers, Brambell et al. (1927-1929) described the 

 changes in the ovary of the mouse for a period of approximately six 

 months after irradiation. The possibility that the regenerative changes 

 lead to neoplasia was then unsuspected. Irradiated mice may undergo 

 several pregnancies, yet develop ovarian neoplasms a year and a half 

 after irradiation (Furth, 1949; Deringer et al., 1953). The induction 

 period of the tumors is invariably long. While regenerative changes 

 begin, depending on total dose after four to six months, tumorlike 

 growths do not appear before about seven months; large tumors are 

 infrequent and metastases are rare. 



In the first study describing the induction of ovarian tumors by X 

 radiation (Furth and Furth, 1936) mice of three different strains were 

 exposed to a single dose or repeated large doses of X radiation at the age 

 of approximately five to twelve weeks. Irradiation caused a fifteenfold 

 increase of ovarian tumors over that of controls. Following irradiation 

 of four- to six- weeks-old mice with single doses of 87, 175, or 350 r of X 

 radiation (Furth and Boon, 1943), ovarian tumors began to appear when 

 the mice were about eleven months of age. The frequency of these neo- 

 plasms increased with time and almost every mouse that lived seventeen 

 months developed a unilateral or bilateral ovarian growth, irrespective of 

 the dose of radiation. 



The observation that total-body irradiation in female mice is fre- 

 quently, if not inevitably, followed by the development of ovarian tumors 

 has been described by numerous investigators (Bali and Furth, 1949). 

 Lorenz et al. (1947) pointed out that, in mice chronically exposed to 0.1 r 

 daily (8 hours), there is a significant increase in ovarian tumor incidence 

 over that of controls. The maximum accumulated dose was 164 r. 

 There is no significant decrease in mean survival time. Thus the ovarian 

 tumor-inducing dose is cumulative and the smallest dose rate inducing 

 ovarian tumors in mice is about 0.1 r daily, with an average total dose of 

 110 r. 



Exposure of ovaries to X radiation causes the development of tumors 

 (Fig. 18-8) of different types. These neoplasms are multicentric, occur 

 frequently in both ovaries, and are of diverse histological type, each of 

 which can be isolated as a pure line by serial transplantation. Most 



