OXIDATIVE METABOLISM OF CARCINOGENS BY TROUT LIVER RESULTING IN PROTEIN BINDING AND MUTAGENICITY

Protein binding of benzo(α)pyrene and mutagenicity resulting from metabolic activation by trout liver microsomal mixed function oxidase was investigated. The metabolite pattern produced by the relatively active benzo(α)pyrene hydroxylase of trout liver microsomes was established by HPLC and compared with that produced by rat liver microsomes. Three dihydrodiols, quinones and two phenols of benzo(α)pyrene were detected as well as indications of other, unidentified metabolites. The pathway of production of some of the metabolites is apparently via reactive intermediates which bind covalently to protein. Like in the mammalian system the intermediates seem to include epoxides as the inhibition of epoxide hydratase results in a relative increase in covalently bound benzo(α)pyrene. Trout liver microsomal mixed function oxidase results in formation of mutagenic intermediates from benzo(α)pyrene, aflatoxin B1 and 2-acetylaminofluorene.