Adrenal mediation of ethanol's inhibition of benzo[a]pyrene metabolism

Abstract

Previous studies in rats have demonstrated that acute ethanol (1 h) at high doses inhibits xenobiotic metabolism and that the effect is modulated by the adrenals. In this paper, we report a similar phenomenon for benzo[a]pyrene (BaP) metabolism but the inhibitory effect is restricted to detoxication without effect on activation routes. Rats were administered ethanol (5 g/kg) orally and sacrificed 1 h later. Microsomes were isolated and assayed for capacity to metabolized BaP to activated and detoxified products. Ethanol treatment inhibited detoxication, as evidenced by approximately 50% decrease in 3‐hydroxy‐BaP formation. There was little effect on metabolic routes forming activated products, as indicated by no change in the rate of dihydrodiol formation. To determine the role of the adrenals in ethanol's inhibitory effect towards detoxication, a similar experiment was performed in adrenalectomized (ADX) rats. ADX alone slightly decreased 3‐hydroxy‐BaP formation, but treatment with ethanol resulted in no significant differences from ADX controls. Corticosterone administration to ADX rats resulted in an inhibition of the formation of all metabolites. The data suggest that acute ethanol inhibits the detoxication of BaP without effecting activation and that this effect is mediated by the adrenals. This would be expected to increase the proportion of carcinogenic metabolites.