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The Effect of Gonadectomy on the Development of Hepatomas Induced by Urethan¹

Division of Oncology, Institute of Medical Research, The Chicago Medical School, Chicago, Illinois 60612

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 C57BL x C3H F₁ 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 treatment, 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 significantly lower (62%) and the ovariectomized group a significantly higher (67%) incidence, as well as size and multiplicity of hepatomas than their corresponding nongonadectomized groups. Morphology of the kidneys of gonadectomized mice primarily indicated a mixed male and female hormonal environment, which was associated with the presence of adrenal cortical hyperplasia and in a few instances with the appearance of adenomas, both of the ß-cell type. Gonadectomy thus practically abolished the sex difference both in the host hormonal environment and hepatoma development.

The results gave indirect evidence that male hormones enhance and female hormones suppress the development of hepatomas but not of the other tumors that were initiated by urethan.

¹ This investigation was supported by Contract PH 43-65-67 from the National Cancer Institute, NIH, USPHS.

Received 2/28/67. Accepted 5/24/67.