Species-specific enhancement by 7,8-benzoflavone of hepatic microsomal metabolism of benzo[e]pyrene 9,10-dihydrodiol to bay-region diol epoxides.
Metabolism of benzo[e]pyrene 9,10-dihydrodiol to the bay-region 9,10-diol-11,12-epoxides by hepatic microsomes from human, rat, mouse, guinea pig, hamster, and rabbit has been examined in the presence and absence of 7,8-benzoflavone. In the absence of 7,8-benzoflavone, the formation of bay-region diol epoxides from benzo[e]pyrene 9,10-dihydrodiol was low in all species except the hamster. With hamster liver microsomes, greater than 60% of total metabolites formed were bay-region diol epoxides, whereas human and mouse liver formed less than 5% of total metabolites as bay-region diol epoxides. Addition of 7,8-benzoflavone to the microsomal incubations stimulated the formation of diol epoxides, but this stimulation was species dependent. The most dramatic stimulation was observed with human and rabbit liver microsomes. In a parallel study, metabolic activation of benzo[e]pyrene 9,10-dihydrodiol to mutagens toward Salmonella typhimurium strain TA 100 by hepatic microsomes from the above species was examined in the presence and absence of 7,8-benzoflavone. In the absence of 7,8-benzoflavone, hepatic microsomes from all the species only weakly activated benzo[e]pyrene 9,10-dihydrodiol to mutagens. 7,8-Benzoflavone enhanced the metabolic activation catalyzed by microsomes from all species except rats and hamsters. Particularly high stimulation was observed with human and rabbit liver microsomes. 9,10-Dihydroxy-9,10,11,12-tetrahydrobenzo[e]pyrene, a compound which cannot be metabolized to a bay-region diol epoxide, was not metabolically activated to mutagenic metabolites in the presence or absence of 7,8-benzoflavone by any of the species examined. These results indicated that the effect of 7,8-benzoflavone on the enhanced mutagenic activity of benzo[e]pyrene 9,10-dihydrodiol is mediated by bay-region diol epoxides, which is consistent with the metabolism studies.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D001580:Benzopyrenes / Q000378:metabolism*; D006224:Cricetinae; D004101:Dihydroxydihydrobenzopyrenes; D005419:Flavonoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009153:Mutagens; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013268:Stimulation, Chemical
C029649:9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene; D001571:Benzoflavones; D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D005419:Flavonoids; D009153:Mutagens; C011512:alpha-naphthoflavone; C022931:9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene