Metabolism of 8-hydroxymethylbenz[a]anthracene by rat liver microsomes. Stereochemistry of dihydrodiol metabolites and the effect of enzyme induction.

Metabolism of the carcinogen 8-hydroxymethylbenz[a]anthracene (8-HOCH2-BA) with liver microsomes from 3-methylcholanthrene-treated rats resulted in 12 identifiable metabolites. Trans-1,2-, 3,4-5,6-, 8,9-, and 10,11-dihydrodiols are among the identified metabolites. The major enantiomers of the trans-dihydrodiols have 1R,2R, 3R,4R, 5R,6R, 8S,9S, and 10R,11R absolute configurations, respectively. Metabolites formed by liver microsomes from untreated as well as 3-methylcholanthrene-, phenobarbital-, and polychlorinated biphenyl-treated immature male Sprague-Dawley rats were quantified by using specifically tritium-labeled [3H-CH2]8-HOCH2-BA as the substrate. The identification of an 8,9-dihydrodiol as a metabolite of 8-HOCH2-BA indicates that a hydroxymethyl substituent does not prevent the enzymatic oxidation at the hydroxymethyl-substituted 8,9-double bond of 8-HOCH2-BA. This is the first example of such a dihydrodiol found from the metabolism of a hydroxymethyl-substituted polycyclic aromatic hydrocarbon by rat liver microsomes.