Comparison of epoxide and free-radical mechanisms for activation of benzo[a]pyrene by Sprague-Dawley rat liver microsomes.
Coincubation of [6-3H]benzo[a]pyrene ([6-3H]BP) and [14C]BP with SD rat liver microsomes produced metabolic profiles that showed that the C-6 of BP was not affected by formation of 4,5-dihydro-4,5-dihydroxy-BP, 7,8-dihydro-7,8-dihydroxy-BP, and 9,10-dihydro-9,10-dihydroxy-BP nor the 3- and 9-phenols of BP. Complete retention of tritium at C-6, except in the three quinones, confirmed the radical-cation model for formation of the 6-oxo-radical followed by oxidation to quinones. Epoxide formation at the carcinogenically active regions of BP appeared to biochemically isolate from 6-position activation and suggested that the microsomal epoxide pathway is unrelated to the radicalcation scheme. These molar ratios derived from double-label experiments reinforced the current literature that indicates the epoxide mechanism as the major pathway toward carcinogenic forms of BP.
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D002384:Catalysis; D004852:Epoxy Compounds / Q000494:pharmacology; D005609:Free Radicals; D008658:Inactivation, Metabolic; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011809:Quinones; D051381:Rats
D001580:Benzopyrenes; D004852:Epoxy Compounds; D005609:Free Radicals; D011809:Quinones; D008748:Methylcholanthrene; D006899:Mixed Function Oxygenases; D001579:Benzopyrene Hydroxylase