Syntheses and identification of benzo[c]chrysene metabolites

Like other PAHs, chrysenes are thought to exert their carcinogenicity via m etabolic activation of proximally carcinogenic dihydrodiols to diol epoxide s as ultimate carcinogens. Benzo[c] chrysene (B[c]C) is structurally intrig uing among the PAH because it features both a bay region and a fjord region . Although B[c]C is carcinogenic and mutagenic, few data are available on i ts metabolic activation or the nature of its metabolites. We have synthesized the B[c]C trans-1,2-, 7,8-, and 9,10-dihydrodiols from the appropriate methoxy-substituted bislaphthyl olefins by photochemical cy clization. B[c]C was metabolized with S9 liver fraction from phenobarbital/ beta-naphthoflavone-treated rats. Dihydrodiols were formed on both terminal rings as well as in the K-region. 2-, 3-, and 10-HydroxyB[c]C were also id entified as metabolites. In mutagenicity studies toward S. typhimurium TA10 0, 1,2-dihydrodiol was more mutagenic than B[c]C at doses above 1.25 mu g/p late, whereas 9,10-dihydrodiol was toxic at doses above 1.25 1.25 mu g/plat e.