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 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 synthetase-positive zone of hepatocytes were greater in males than females and were dependent upon the hormonal status of males.
Tokumo
K
K
Division of Pathology and Toxicology, American Health Foundation, Valhalla, NY 10595.
Umemura
T
T
Sirma
H
H
Gebhardt
R
R
Poirier
M C
MC
Williams
G M
GM
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
D004247:DNA; D015073:2-Acetylaminofluorene