title: Mutagenicity, tumor-initiating activity, and metabolism of methylphenanthrenes.
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, only 1,4-dimethylphenanthrene was active in the presence of metabolic activation. Studies on the in vitro metabolism of methylphenanthrenes were performed by incubation of the various isomers with the 9000 X 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 were active when assayed as tumor initiators on mouse skin. In contrast, 1,4-dimethylphenanthrene was found to have potent tumorigenic activity. These results suggest that 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 1,4-dimethylphenanthrene.
mesh_terms: D000818:Animals; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009153:Mutagens; D010616:Phenanthrenes / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D009153:Mutagens; D010616:Phenanthrenes