The effect of gonadectomy on the development of hepatomas induced by urethan.

Exposure of newborn and infant mice to urethan results in a significantly higher incidence of hepatomas in male mice than in females. Sex of the animals, however, does not influence the development of malignant lymphomas, Harderian gland tumors, and lung adenomas. In the present study, the role of gonads in the development of urethan-induced hepatomas and other tumors has been investigated. Seven-day-old O57BL X C3H FI mice of each sex were exposed to the 1st of 6 urethan injections (0.5 mg/gm body weight, each) given at 3-day intervals. Three weeks after the last urethan treat ment, one half of the mice were gonadectomized and the other half were sham-operated. At 52 weeks of age all animals were killed. The sham-operated males developed hepatomas in 96% and the females in 20%. The orchidectomized mice showed a sig nificantly lower (62%) and the ovariectomized group a signifi cantly higher (67%) incidence, as well as size and multiplicity of hepatomas than their corresponding nongonadectomized groups. Morphology of the kidneys of gonadectomized mice pri marily indicated a mixed male and female hormonal environ ment, which was associated with the presence of adrenal corti cal hyperplasia and in a few instances with the appearance of adenomas, both of the ß-eell type. Gonadectomy thus practically abolished the sex difference both in the host hormonal environ ment and hepatoma development. The results gave indirect evidence that male hormones en hance and female hormones suppress the development of hepa tomas but not of the other tumors that were initiated by urethan.