Metabolism and enterohepatic circulation of benzo(a)pyrene-4,5-epoxide in the rat

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Abstract
1. After i.v. administration of 3H-benzo(a)pyrene-4,5-epoxide (32·5 μmol/kg) to rats, 76% of the 3H appeared in bile within 3 h. 2. The glutathione conjugate of benzo(a)pyrene-4,5-epoxide was the major biliary metabolite (33% of dose), together with a glucuronic acid conjugate of benzo(a)pyrene-4,5-diol (18%) and an unidentified metabolite (10%). 3. The glutathione and glucuronic acid conjugates both undergo extensive enterohepatic circulation. Thus, following the intraduodenal administration of the 3H-labelled conjugates, 26% of the radioactivity was excreted in the bile after 24 h in the case of the glutathione derivative, and 40% in the case of the glucuronide. 4. The benzo(a)pyrene-4,5-diol glucuronide, on enterohepatic circulation, appears in the bile in the same form as the conjugate administered with no evidence of further metabolism of the polycyclic hydrocarbon moiety. 5. The glutathione conjugate of benzo(a)pyrene-4,5-epoxide, on recirculation, is re-excreted in bile as one unidentified metabolite, which is susceptible to the action of arylsulphatase.

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