1,2-dihydro-1,2-dihydroxy-5-methylchrysene, a major activated metabolite of the environmental carcinogen 5-methylchrysene.
The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activiation. Significant mutagenic activity was observed primarily in peak E and to a lesser extent in peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hydroxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.
D000818:Animals; D002911:Chrysenes / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009153:Mutagens; D009154:Mutation / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects
D002911:Chrysenes; D009153:Mutagens; D010616:Phenanthrenes; C017229:1,2-dihydro-1,2-dihydroxy-5-methylchrysene; C008422:5-methylchrysene