Evidence for the involvement of a diol-epoxide in the binding of 7,12-dimethylbenz(a)anthracene to DNA in cells in culture.
1,1,1-Trichloropropene 2,3-oxide (TCPO), a known inhibitor of the enzyme epoxide hydrase, inhibits binding of the carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), to the DNA of secondary mouse embryo cell cultures under conditions which do not appreciably decrease the overall metabolism of this carcinogen. This suggests that the formation of a transdihydrodiol is a necessary step in the metabolic pathway leading to DNA binding and that binding probably occurs through the generation of a reactive diol-epoxide. In concert with this, the major DMBA-DNA product  isolated by chromatography on Sephadex LH-20 eluted with a methanol-water gradient is resolved into two separate components in a methanol-sodium borate solution gradient suggesting that, as is known for benzo(a)pyrene, two stereoisomeric diol-epoxides are involved in the binding of DMBA to DNA.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D004247:DNA / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D004852:Epoxy Compounds / Q000378:metabolism / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology; D051379:Mice; D008968:Molecular Conformation; D013997:Time Factors
D001551:Benz(a)Anthracenes; D004852:Epoxy Compounds; D006843:Hydrocarbons, Chlorinated; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D004851:Epoxide Hydrolases