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.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D001551:Benz(a)Anthracenes; D002273:Carcinogens; C031255:8-methylbenzanthracene; D010130:p-Aminohippuric Acid