TY - JOUR T1 - Oxidative metabolites of 7,12-dimethylbenz[a]anthracene. Further investigation of the K-region epoxide. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 28 LP - 33 VL - 8 IS - 1 AU - L K Wong AU - C L Wang AU - F B Daniel Y1 - 1980/01/01 UR - http://dmd.aspetjournals.org/content/8/1/28.abstract N2 - Metabolism of 7,12-dimethylbenz[a]anthracene in rat liver 10,000 g supernatant fraction has been examined by combined gas chromatography-mass spectrometry subsequent to high-pressure liquid-chromatographic separation of the incubation mixture. In addition to the mono-, di-, and trihydroxylated oxidative metabolites usually associated with the biotransformation of polycyclic aromatic hydrocarbons, we observed the formation of a methanolysis product from the K-region epoxide intermediate during the workup procedure. The identification of this compound provides a direct evidence for the presence of the K-region epoxide in the metabolism mixture, and it serves as a convenient means to assay for this metabolite. Moreover, we detected the methanolysis derivative only from the K-region epoxide but none from the non-K-region counterparts. This finding suggests that the non-K-region epoxides undergo facile enzymatic and nonenzymatic hydrolysis and/or rearrangement reactions as soon as they are produced. On the other hand, the K-region epoxide possesses greater stability. It can remain longer in a metabolism mixture and react with methanol subsequently. ER -