CARCINOGENESIS BY IONIZING RADIATIONS 1171 



available information is certainly not impressive. The assumed period of 

 latency was so short in many reported cases that many neoplasms may 

 have been present at the time of irradiation. However, the denial of the 

 theoretical possibility of such an event (Dehler, 1927) certainly lost its 

 wisdom in the light of later experimental findings on the induction of 

 neoplasms in the reproductive organs of animals. Nevertheless, the 

 clinical observations of Depenthal (1919), Bumm (1923), Vogt (1926), 

 and Dehler (1927) should be regarded as possibilities rather than proof 

 of the induction of neoplasm in reproductive organs of women (uterus, 

 ovary, vulva). 



Pituitary Tumors. Large quantities of I 131 (200-400 nc in mice) com- 

 pletely destroy the thyroid gland. Persistent lack of thyroid hormone 

 causes an over-stimulation of the pituitary gland and the hyperplasia of 

 the pituitary cells, which secrete thyrotropic hormones, gradually 

 terminates in neoplastic growth. 



The original findings of Gorbman (1949) that the destruction of the 

 thyroid by I 131 gives rise in mice to such growths have been fully con- 

 firmed, every mouse receiving doses of I 131 large enough to destroy the 

 thyroid and surviving such treatment longer than thirteen months 

 developed pituitary tumors (Furth and Burnett, 1951). In line with this 

 interpretation are the few observations that long-continued administra- 

 tion of antithyroid compounds may cause the development of similar 

 tumors. 



The pituitary growths induced by doses of I 131 destructive to the 

 thyroid are readily transplantable in mice, the thyroid glands of which 

 have been similarly destroyed, but not in normal mice, with rare excep- 

 tions. Therefore, these growths are not fully autonomous but merely 

 conditioned neoplasms even though they may metastasize. Pituitary 

 enlargement after thyroid destruction by I 131 can be prevented by admin- 

 tration of 0.15 per cent USP desiccated thyroid in diet (thyroxine) (Gold- 

 berg and Chaikoff, 1951b); similarly, thyroid hormone restrains the 

 growths of the grafted pituitary tumors. These tumors discharge thyro- 

 tropic and possibly gonadotropic hormones and, when grafted in young 

 mice, cause a tremendous cystic dilatation of the extrahepatic biliary 

 tract (Furth et al., 1952). While a study of these tumors is of great 

 interest in both endocrinology and oncology, it is not likely to become a 

 human problem. When patients with thyroid carcinoma are given 

 thyroid-destructive doses of I 131 , and the symptoms of hypothyroidism 

 become pronounced, thyroid hormone is administered, which counteracts 

 the stimulation of the pituitary gland. 



Thyroid. Administration of I 131 localizes predominantly in the thyroid 

 gland, and thus 300-400 /zc given to mice causes complete destruction of 

 the gland. Somewhat lower doses (200-300 /*c) destroy the gland, leav- 

 ing a few atypical acini which do not seem to respond to excessive amounts 



