Metabolic and Structural Requirements for the Carcinogenic Potencies of Unsubstituted and Methyl-Substituted Polycyclic Aromatic Hydrocarbons

摘要: Extensive metabolism studies of many non-K-region dihydro-diols unsubstituted and methyl-substituted polycyclic aromatic hydrocarbons (PAHs) by mammalian drug-metabolizing enzymes indicate that the extent formation vicinal dihydrodiol-epoxides is determined conformations geometric location adjacent double bond dihydrodiol precursors. Unsubstituted PAH dihydrodiols with one (in case cis-dihydrodiols) or both trans-dihydrodiols) hydroxyl groups preferentially in quasi- equatorial can be further metabolized to di- hydrodiol-epoxides. The trans-dihydrodiols exclusively quasi-diaxial. also enzymatically epoxidized form dihydrodiol-epox- ides, but these formations highly dependent on dihydrodiols. Quasi-diaxial an at bay-regions are not minimally dihydrodiol-epoxides. A methyl substituent hydroxylated carbons bonds quasi-diequatorial substantially completely inhibit dihydrodiol-epoxide formations. These findings, along bay-region theory, provide molecular basis for observed carcinogenic potencies containing PAHs.