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Inhibition by gonadectomy of effects of 2-acetylaminofluorene in livers of male, but not female rats
Division of Pathology and Toxicology, American Health Foundation 1 Dana Road, Valhalla, NY 10595, USA
1Visiting scientist from First Department of Internal Medicine, Medical School of Hiroshima University Hiroshima, Japan
2Visiting scientist from Division of Toxicology, National Institute of Hygienic Sciences Tokyo, Japan
3Present address: Physiologisch-Chemisches Institut der Universität Tübingen Tübingen, Germany
4Present address: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health Bethesda, MD 20892, USA
The influence of gonadectomy on the effects of 2-acetylamino-fluorene (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 body wt. AAF was administered either with no pretreatment or beginning 4 weeks after gonadectomy, which was performed at 5 weeks of age. In male rats AAF induced a large number of placental glutathione S-transferase foci in livers by 8 weeks, while in female rats the number was about 10% of that in males. Orchidectomy decreased the AAF induction of foci in male rats by 60%, whereas ovariectomy had no effect in female rats. Similarly, orchidectomy decreased DNA adduct levels approximately 85% in male rats given AAF by gavage for 4 weeks. In ovariectomized female rats at 4 and 8 weeks hepatic DNA adduct levels were somewhat elevated (<50%) as compared to intact controls. The zone of glutamine synthetase-positive hepatocytes around the central vein was reduced by AAF exposure of male, but not female, rats. Male rats displayed a larger zone than females and the zone in males was reduced to the level of females by orchidectomy. Orchidectomy also diminished the effect of AAF on glutamine synthetase-positive cells. Thus, the induction of neoplastic conversion by AAF in rat liver, the extent of DNA adduct formation and the reduction of the glutamine synthetasepositive zone of hepatocytes were greater in males than females and were dependent upon the hormonal status of males.
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