Inhibition by gonadectomy of effects of 2-acetylaminofluorene in livers of male, but not female rats.

TY - JOUR

T1 - Inhibition by gonadectomy of effects of 2-acetylaminofluorene in livers of male, but not female rats.

AU - Tokumo, K

AU - Umemura, T

AU - Sirma, Hüseyin

AU - Gebhardt, R

AU - Poirier, M C

AU - Williams, G M

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 14

SP - 1747

EP - 1750

JO - CARCINOGENESIS

JF - CARCINOGENESIS

SN - 0143-3334

IS - 9

M1 - 9

ER -