Influence of Hormones on N-2-Fluorenyldiacetamide-Induced Hyperplastic Hepatic Nodules in Rats2

Abstract

Inbred A × C male rats 12 weeks old were given 0.025% N-2-Ruorenyldiacetamide in their diet for 4-week periods alternately with 1 week on the basal diet until the carcinogen was administered for 16 weeks. In a group of rats killed after 23 weeks, almost all had developed hyperplastic hepatic nodules. The hormonal status was altered in other groups of animals after 23 weeks to determine if the progression of the nodules to carcinomas was influenced. Intact control animals without changes in hormones developed carcinomas of the liver when killed at the end of 48 weeks. The lesions in adrenalectomized rats or those adrenalectomized and given either cortisone or deoxycorticosterone did not differ from the control animals. The incidence of carcinomas and metastases was decreased by hypophysectomy, adrenalectomy plus castration, castration, or thyroidectomy at 23 weeks. By contrast, the number of carcinomas per liver and the number of undifferentiated (as compared with differentiated) carcinomas were increased in castrated rats given testosterone or diethylstilbestrol. The changes in the progression of hyperplastic nodules to carcinomas, except for castrated rats given diethylstilbestrol or adrenalectomized rats given deoxycorticosterone, were similar to those observed previously in animals in which the hormones were altered simultaneously with administration of the carcinogen. It is concluded that this progression depends on hormones of the host, particularly testosterone.