STUDY OF CHEMICAL CARCINOGENESIS .9. 1,2-DIHYDRO-1,2-DIHYDROXY-5-METHYLCHRYSENE, A MAJOR ACTIVATED METABOLITE OF ENVIRONMENTAL CARCINOGEN 5-METHYLCHRYSENE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (7) , 2191-2194
Abstract
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 .times. g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into 9 peaks, A to I. Each peak was collected and tested for mutagenicity with activation. 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.