Oxidative metabolites of 7,12-dimethylbenz[a]anthracene. Further investigation of the K-region epoxide.
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.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats
D001551:Benz(a)Anthracenes; D004852:Epoxy Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene