Syntheses and Identification of Benzo[C]Chrysene Metabolites

Like other PAHs, chrysenes are thought to exert their carcinogenicity via metabolic activation of proximally carcinogenic dihydrodiols to diol epoxides as ultimate carcinogens. Benzoc] chrysene (Bc]C) is structurally intriguing among the PAH because it features both a bay region and a fjord region. Although Bc]C is carcinogenic and mutagenic, few data are available on its metabolic activation or the nature of its metabolites.

We have synthesized the Bc]C trans-1,2-, 7,8-, and 9,10-dihydrodiols from the appropriate methoxy-substituted bisnaphthyl olefins by photochemical cyclization. Bc]C was metabolized with S9 liver fraction from phenobarbital/β-naphthoflavone-treated rats. Dihydrodiols were formed on both terminal rings as well as in the K-region. 2-, 3-, and 10-HydroxyBc]C were also identified as metabolites. In mutagenicity studies toward S. typhimurium TA100, 1,2-dihydrodiol was more mutagenic than Bc]C at doses above 1.25 μg/plate, whereas 9,10-dihydrodiol was toxic at doses above 1.25 μg/plate.