Metabolism of 7,12-dimethylbenz[a]anthracene and its methyl-hydroxylated metabolites: formation of phenolic metabolites at the 2-positions. |
| |
Authors: | M W Chou G D Easton S K Yang |
| |
Affiliation: | Department of Pharmacology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20014 USA |
| |
Abstract: | ![]() The 1- and 2-positions of 7,12-dimethylbenz[a]anthracene (DMBA) were thought not to be involved in biotransformation to 1,2-epoxide and 1,2-dihydrodiol because of steric hindrance from the 12-methyl group (Biochem. Biophys. Res. Commun. : 357–362, 1978). However, we have identified four 2-phenols as rat liver microsomal metabolites of DMBA and its methyl-hydroxylated metabolites, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]-anthracene, and 7,12-dihydroxymethylbenz[a]anthracene. Our findings suggest that neither the 12-methyl group nor the 12-hydroxymethyl group blocks the microsomal oxygenations of the 1,2 positions of DMBA or its methyl-hydroxylated derivatives. The 2-phenols may be formed as nonenzymatic rearrangement products of the 1,2-epoxide intermediates, although their formations by a direct hydroxylation mechanism cannot be ruled out. |
| |
Keywords: | To whom correspondence should be addressed. |
本文献已被 ScienceDirect 等数据库收录! |
|