INHIBITION BY GONADECTOMY OF EFFECTS OF 2-ACETYLAMINOFLUORENE IN LIVERS OF MALE, BUT NOT FEMALE RATS

The influence of gonadectomy on the effects of 2-acetylaminofluorene ( AAF) in the livers of rats was studied. Groups of male and female F344 rats at 9 weeks of age were given AAF by daily gavage 5 days per week for 4 or 8 weeks for total cumulative doses of 1.0 or 2.0 mmol/kg bod y wt. AAF was administered either with no pretreatment or beginning 4 weeks after gonadectomy, which was performed at 5 weeks of age. In mal e rats AAF induced a large number of placental glutathione S-transfera se foci in livers by 8 weeks, while in female rats the number was abou t 10% of that in males. Orchidectomy decreased the AAF induction of fo ci in male rats by 60%, whereas ovariectomy had no effect in female ra ts. Similarly, orchidectomy decreased DNA adduct levels approximately 85% in male rats given AAF by gavage for 4 weeks. In ovariectomized fe male rats at 4 and 8 weeks hepatic DNA adduct levels were somewhat ele vated (< 50%) as compared to intact controls. The zone of glutamine sy nthetase-positive hepatocytes around the central vein was reduced by A AF exposure of male, but not female, rats. Male rats displayed a large r zone than females and the zone in males was reduced to the level of females by orchidectomy. Orchidectomy also diminished the effect of AA F on glutamine synthetase-positive cells. Thus, the induction of neopl astic conversion by AAF in rat liver, the extent of DNA adduct formati on and the reduction of the glutamine synthetase-positive zone of hepa tocytes were greater in males than females and were dependent upon the hormonal status of males.