Mutagenicity of the bay-region diol-epoxides and other benzo-ring derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene.
The mutagenic activities of dibenzo(a,h)(pyrene, dibenzo(a,i)pyrene, and a total of 11 of their benzo-ring derivatives were evaluated in bacterial and mammalian cells in the absence or presence of a mammalian metabolic activation system. trans-1,2-Dihydroxy-1,2-dihydrodibenzo(a,h)pyrene and trans-3,4-dihydroxy-3,4-dihydrodibenzo(a,i)pyrene, the expected dihydrodiol precursors of bay-region diol-epoxides, were metabolized to products which were more mutagenic to strains TA98 and TA100 of Salmonella typhimurium than were the metabolic products formed from their respective parent hydrocarbons. For each dihydrodiol, replacement of the benzo-ring double bond adjacent to the diol moiety with a single bond resulted in tetrahydrodiol derivatives which could not be metabolically activated, suggesting that one or both diastereomeric bay-region diol-epoxides were the bioactivated metabolites. The authentic bay-region diol-epoxide diastereomers of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene in which the benzylic hydroxyl group and the epoxide oxygen are trans (diol-epoxide 2 series) were highly mutagenic in strains TA98 and TA100 of S. typhimurium and in cultured Chinese hamster V79 cells. Neither diol-epoxide was significantly, if at all, metabolized by epoxide hydrolase. The bay-region diol-epoxide of dibenzo(a,i)pyrene was from 1.5 to 5 times more active as a mutagen than the diol-epoxide of dibenzo(a,h)pyrene, and in strain TA98 of S. typhimurium as well as Chinese hamster V79 cells, it had activity comparable to that of the highly carcinogenic bay-region diol-epoxide of benzo(a)pyrene.
D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000494:pharmacology; D004101:Dihydroxydihydrobenzopyrenes; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D007536:Isomerism; D008862:Microsomes, Liver / Q000201:enzymology; D009153:Mutagens; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; C021146:dibenzo(a,i)pyrene; C031197:3,4-dihydro-3,4-dihydroxybenzo(a,i)pyrene; C031196:1,2-dihydro-1,2-dihydroxydibenzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; C031195:dibenzo(a,h)pyrene