Syntheses and identification of benzo[c]chrysene metabolites

Dhimant Desai, Jacek Krzeminski, Jyh Ming Lin, Anju Chadha, Naoki Miyata, Haruhiko Yagi, Donald M. Jerina, Shantu Amin

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Abstract

Like other PAHs, chiysenes are thought to exert their carcimogenicity via metabolic activation of proximally carcinogenic dihydrodiols to diol epoxides as ultimate carcinogens. Benzo[c] chrysene (B[c]C) is structurally intriguing 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 its 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 bisnaphthyl olefins by photochemical cyclization. B[c]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-HydroxyB[c]C were also identified as metabolites. In mutagenicity studies toward S. typhimurium TA100, 1,2-dihydrodiol was more mutagenic than B[c]C at doses above 1.25 μg/plate, whereas 9,10-dihydrodiol was toxic at doses above 1.25 μg/plate.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalPolycyclic Aromatic Compounds
Volume16
Issue number1-4
Publication statusPublished - Dec 1 1999

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All Science Journal Classification (ASJC) codes

  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

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