Ovariectomy promotes the growth of altered hepatic foci after withdrawal and reintroduction of phenobarbital during hepatocarcinogenesis in rats.

Female F344/N rats were given 70% partial hepatectomies and intubated with diethyl-nitrosamine (DEN, 10 mg/kg) 24 hours later. They were fed a cereal-based diet, NIH-07 (NIH) + 0.05% phenobarbital (PB) for 6 months, at which time NIH + PB was withdrawn and the rats were ovariectomized (OV) or sham-operated (SH). Groups of 7-10 rats were fed a semipurified diet (AIN-76) for 1 or 2 months after withdrawal of NIH + PB, or NIH + PB for 2 months, or AIN-76 diet for 1 month and subsequently NIH + PB for 1 month. Placental glutathione S-transferase (PGST)- and gamma-glutamyltransferase (GGT)-positive (+) altered hepatic foci (AHF) were analysed by quantitative stereology. Ovariectomy stimulated growth of AHF after withdrawal and reintroduction of NIH + PB. AHF, especially PGST+ AHF, continued to regress throughout the PB withdrawal period in rats fed AIN-76 diet. In most studies of chemical hepatocarcinogenesis, females have been shown to develop a greater volume of AHF than males. In our study, however, ovariectomy stimulated the growth of AHF after withdrawal and reintroduction of PB. Because AHF occurring spontaneously in male rats develop more rapidly than in female rats, the greater rate of growth of AHF in OV female rats may reflect a similar mechanism.