Tumor-initiating activity of major in vivo metabolites of indeno[1,2,3-cd]pyrene on mouse skin

Carcinogenesis
J E RiceJ C Wiley

Abstract

Indeno[1,2,3-cd]pyrene is a ubiquitous environmental pollutant which is active as a tumor initiator and complete carcinogen on mouse skin and is carcinogenic in rat lung. The major metabolites of indeno[1,2,3-cd]pyrene as formed in vivo in mouse skin have been identified. 8-Hydroxyindeno[1,2,3-cd]pyrene is the most abundant metabolite identified. 9-Hydroxyindeno[1,2,3-cd]pyrene and trans-1,2-dihydro-1,2-dihydroxyindeno[1,2,3-cd]pyrene are also major in vivo metabolites in mouse skin. Several minor metabolites were also identified. Among these are trans-1,2-dihydro-1,2,8-trihydroxyindeno[1,2,3-cd]pyrene, trans-1,2-dihydro-1,2,9-trihydroxyindeno[1,2,3-cd]pyrene, indeno[1,2,3-cd]pyrene-1,2-dione, and 10-hydroxyindeno[1,2,3-cd]pyrene. The tumor-initiating activity of several of the major in vivo metabolites of indeno[1,2,3-cd]pyrene has been investigated on mouse skin. Trans-1,2-dihydro-1,2-dihydroxyindeno[1,2,3-cd]pyrene and 1,2-dihydro-1,2-epoxyindeno[1,2,3-cd]pyrene both produced an 80% incidence of tumor-bearing mice at a total initiating dose of 1.0 mg. The activity of this K-region dihydrodiol and K-region oxide was, however, less than that of the parent hydrocarbon. These data suggest that 1,2-dihydro-1,2-epoxyindeno[1,2,3-c...Continue Reading

Citations

May 20, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Camille GeniesThierry Douki

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