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Effects of the polycyclic aromatic hydrocarbon heterocycles, carbazole and dibenzothiophene, on in vivo and in vitro cypia activity and polycyclic aromatic hydrocarbon-derived embryonic deformities

Authors

  • Deena M. Wassenberg,

    Corresponding author
    1. Nicholas School of the Environment and Earth Sciences and Integrated Toxicology Program, Box 90328, Duke University, Durham, North Carolina 27708, USA
    • Nicholas School of the Environment and Earth Sciences and Integrated Toxicology Program, Box 90328, Duke University, Durham, North Carolina 27708, USA
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  • Abby L. Nerlinger,

    1. University of Notre Dame Department of Biology, Notre Dame, Indiana 46556, USA
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  • Lauren P. Battle,

    1. Nicholas School of the Environment and Earth Sciences and Integrated Toxicology Program, Box 90328, Duke University, Durham, North Carolina 27708, USA
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  • Richard T. Di Giulio

    1. Nicholas School of the Environment and Earth Sciences and Integrated Toxicology Program, Box 90328, Duke University, Durham, North Carolina 27708, USA
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Abstract

Herocyclic derivatives of polycyclic aromatic hydrocarbons (PAHs) are often significant components of environmental contaminant mixtures; however, their contribution to the toxicity of these mixtures is not well characterized. These heterocycles commonly co-occur in PAH mixtures, which contain agonists for the aryl hydrocarbon receptor (AHR). Our goal for these studies was to explore the effects of two PAH heterocycles, carbazole (CB) and dibenzothiophene (DBT), alone and in combination with a PAH-type agonist for the AHR (β-naphthoflavone [BNF]) on AHR-mediated cytochrome P4501A (CYP1A) activity and on fish embryotoxicity. Embryos of Fundulus heteroclitus were exposed to CB or DBT, with and without coexposure to BNF. Carbazole alone slightly induced, whereas DBT alone slightly reduced, in ovo CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activity compared to control values. However, exposure to CB or DBT reduced in ovo EROD activity in embryos coexposed to BNF. Carbazole and DBT were characterized in vitro as noncompetitive CYP1A inhibitors. Carbazole and DBT enhanced the embryotoxicity of BNF, although neither compound was embryotoxic by itself. The co-occurrence of CB and DBT with PAH-type AHR inducers in contaminated ecosystems may increase the toxicity of PAH-type AHR agonists in these settings and may need to be considered when estimating the embryotoxicity of PAH mixtures.

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