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

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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. A similar phenomenon for benzo[a]pyrene (BaP) metabolism was reported but the inhibitory effect was restricted to detoxification 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 .apprx. 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. Acute ethanol inhibited the detoxication of BaP without effecting activation and this effect was mediated by the adrenals. This probably would increase the proportion of carcinogenic metabolites.