MUTAGENICITY, TUMOR-INITIATING ACTIVITY, AND METABOLISM OF METHYLPHENANTHRENES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (9) , 3441-3447
Abstract
The mutagenicity, in vitro metabolism and tumor-initiating activity of methylphenanthrenes were evaluated. The only monomethyl isomers which were mutagenic toward Salmonella typhimurium were 1- and 9-methylphenanthrenes. Among the disubstituted phenanthrenes assayed for mutagenicity on 1,4-dimethylphenanthrene was active in metabolic activation. Studies on the in vitro metabolism of methylphenanthrenes were performed by incubation of the various isomers with the 9000 .times. g supernatant from Aroclor-treated rat livers. Comparison of mutagenicity with metabolites formed in vitro indicated that inhibition of 9,10-dihydrodiol formation was positively associated with mutagenic activity. Among the metabolites of 1- and 9-methylphenanthrenes, significant mutagenic activity was associated only with the 3,4- and/or 5,6-dihydrodiol. Metabolism to the 1,2- or 7,8-dihydrodiol, the requisite dihydrodiols for formation of bay-region dihydrodiol-epoxides, was most significant in the case of 4-methylphenanthrene. None of the isomeric methylphenanthrenes was active when assayed as a tumor initiator on mouse skin. 1,4-Dimethylphenanthrene had potent tumorigenic activity. Inhibition of 9,10-dihydrodiol formation, the influence of a 4-methyl substituent in directing dihydrodiol formation at the 1,2- or 7,8-positions and the presence of a bay-region methyl group may be responsible for eliciting a tumorigenic response for dimethylphenanthrene.