The association of bacterial mutagenicity of hydrocarbon-derived 'bay-region' dihydrodiols with the Iball indices for carcinogenicity and with the extents of DNA-binding on mouse skin of the parent hydrocarbons.
The mutagenic activities of benz[alpha]anthracene, 7-methylbenz[alpha]anthracene, 7,12-dimethylbenz[alpha]anthracene, 3-methylcholanthrene and benzo[alpha]pyrene, together with those of the trans-dihydrodiols derived from these hydrocarbons that would be expected to yield 'bay-region' vicinal diolepoxides on further metabolism have been examined in assays with S. typhimurium TA100 using post-mitochondrial supernatant fractions prepared from the livers of 3-methylcholanthrene-treated rats. Mutagenic activities obtained have been compared with: (a) the extents of reaction with DNA that occur in mouse skin following treatment with these hydrocarbons; (b) the carcinogenicities of the hydrocarbons expressed as Iball indices; (c) their activities as tumour-initiating agents on mouse skin. Close positive associations were found between the microsome-mediated mutagenicities of the dihydrodiols that could yield "bay-region" diol-epoxides and: (a) the extents of reaction with DNA in hydrocarbon-treated mouse skin; (b) the carcinogenic potencies of the parent hydrocarbons; although these correlations are not perfect, the mutagenic activities of the hydrocarbons themselves in microsome-mediated assays with S. typhimurium show no correlation with their extents of DNA binding on mouse skin and a poor correlation with their activities as initiating agents. These comparisons also indicated a statistically-significant positive correlation between carcinogenicity and the in vivo DNA binding on mouse skin treated with the hydrocarbons. Differences in the metabolic pathways by which polycyclic hydrocarbons are activated in vivo and in vitro are discussed in relation to the improved correlations found with the dihydrodiols.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens; D004247:DNA / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; D011083:Polycyclic Compounds; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA