Inhibitory effect of antiestrogen on hepatic tumorigenesis in WF rats treated with diethylstilbestrol alone or in combination with N-nitrosobutylurea.

Four groups of inbred male WF rats were castrated and received sc implantations of diethylstilbestrol [(DES) CAS: 56-53-1; alpha,alpha'-diethyl-4,4'-stilbenediol] at 40 days of age. Group I was given no further treatment; groups II and IV were treated with antiestrogen (AntiE) clomiphene citrate simultaneously with DES treatment. At 50-55 days of age, groups III and IV were given drinking water containing N-nitrosobutylurea [(NBU) CAS: 869-01-2; 1-butyl-1-nitrosourea] for 30 days. Castrated male rats or rats castrated and treated with NBU alone developed neither hepatic tumors (HT) nor pituitary tumors (PT). When AntiE was administered, incidences of HT and PT, size and the total number of HT, and mean pituitary weight were significantly reduced in rats given DES alone and in rats given DES with NBU. AntiE treatment changed the distribution in the histologic classification of hepatocellular lesions: Neoplastic nodules, instead of hepatocellular carcinomas, were predominant. The results indicate that AntiE was effective in the inhibition of hepatic and pituitary tumorigenesis associated with DES treatment. Our previous study has shown that prolactin was not involved in this hepatic tumorigenesis. Therefore, these studies provide evidence that the carcinogenic effect of DES on the liver cell is direct and that HT are regulated in development and growth by AntiE treatment.