A Metabolic Activation Mechanism of 7 H -Dibenzo[ c,g ]carbazole Via o -Quinone. Part 1: Synthesis of 7 H -Dibenzo[ c,g ]carbazole-3,4-dione and Reactions with Nucleophiles |
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| Authors: | Weiling Xue David Warshawsky Mark Rance Koka Jayasimhulu |
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| Affiliation: | 1. Department of Environmental Health , University of Cincinnati , Cincinnati , Ohio , USA;2. Department of Molecular Genetics, Biochemistry and Microbiology , University of Cincinnati , Cincinnati , Ohio , USA;3. Department of Chemistry , University of Cincinnati , Cincinnati , Ohio , USA |
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| Abstract: | 7 H -Dibenzo c,g ]carbazole (DBC) is a potent carcinogen present in the environment. The metabolic activation pathway of DBC has not been completely understood. The formation of the DBC- o -quinone was proposed and the novel DBC-3,4-dione was chemically synthesized from 4-OH- or 3-OH-DBC, using the Fremy's salt at room temperature. The DBC-3,4-dione was found to react readily with model nucleophile, 2-mercaptoethanol, to afford 1-(2'-hydroxyethylthio)-DBC-3,4-dione through 1,4-Michael addition. An adduct of DBC-3,4-dione with adenine was obtained; adducts formed with other DNA bases and nucleosides were partially characterized and are under further analysis. Under the same conditions, DBC-3,4-dione with guanine did not yield an adduct. These results are encouraging for further studies on DNA binding of DBC through 3,4-dione in vitro and in vivo. |
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| Keywords: | 7 H -dibenzo[ c g ]carbazole-3 4-dione 7 H -dibenzo[ c g ]carbazole Dna Adducts 1 4-Michael Addition o -quinone |
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