Comparison of the genotoxic activities of the K-region dihydrodiol of benzo[a]pyrene with benzo[a]pyrene in mammalian cells: morphological cell transformation; DNA damage; and stable covalent DNA adducts.

摘要: Abstract Benzo[ a ]pyrene (B[ ]P) is the most thoroughly studied polycyclic aromatic hydrocarbon (PAH). Many mechanisms have been suggested to explain its carcinogenic activity, yet many questions still remain. K-region dihydrodiols of PAHs are metabolic intermediates depending on specific cytochrome P450 and had thought be detoxification products. However, several recently shown morphologically transform mouse embryo C3H10T1/2CL8 cells (C3H10T1/2 cells). Because not metabolically formed from by C3H10T1/2 cells, these provide useful tool independently study action their dihydrodiols. Here, we compare morphological cell transforming, DNA damaging, adducting activities dihydrodiol B[ ]P, trans- ]P-4,5-diol with ]P. Both trans -B[ ]P transformed producing both Types II III foci. The transforming cytotoxicity dose response curves for were indistinguishable. Since transformation strongly associated mutation and/or larger scale damage in identification induced was sought. exhibited significant damaging activity without concurrent using comet assay, but different responses tail distributions. adduct patterns examined after or treatment 32 P -postlabeling techniques improved TLC elution systems designed separate polar adducts. While produced one major identified as anti-trans ]P-7,8-diol-9,10-epoxide-deoxyguanosine, no stable covalent adducts detected ]P-4,5-diol-treated cells. In summary, this provides evidence absence induce transformation, agents differ, qualitatively quantitatively. concert other PAHs, data suggest new mechanism/pathway metabolites.