Effects of the polycyclic aromatic hydrocarbon heterocycles, carbazole and dibenzothiophene, on in vivo and in vitro cyp1a activity and polycyclic aromatic hydrocarbon-derived embryonic deformities

• Published in: Environmental toxicology and chemistry Vol. 24; no. 10; pp. 2526 - 2532
• Main Authors: WASSENBERG, Deena M, NERLINGER, Abby L, BATTLE, Lauren P, DI GIULIO, Richard T
• Format: Journal Article
• Language: English
• Published: Pensacola, FL SETAC 01-10-2005
• Subjects: Animal, plant and microbial ecology; Animals; Applied ecology; Biological and medical sciences; Carbazoles - toxicity; Carcinogens - toxicity; Congenital Abnormalities - etiology; Congenital Abnormalities - veterinary; Cytochrome P-450 CYP1A1 - drug effects; Cytochrome P-450 CYP1A1 - metabolism; Drug Interactions; Ecotoxicology, biological effects of pollution; Embryo, Nonmammalian; Enzyme Induction; Fundamental and applied biological sciences. Psychology; Fundulidae - embryology; Fundulus heteroclitus; General aspects; Receptors, Aryl Hydrocarbon - drug effects; Receptors, Aryl Hydrocarbon - physiology; Thiophenes - toxicity; Cytochrome; In vivo; Ecotoxicology; Hydrocarbon; Toxicity; Carbazole Dibenzothiophene Embryotoxicity Cytochrome P4501A Polycyclic aromatic hydrocarbons; Polycyclic aromatic compound; Organic compounds
• ISSN: 0730-7268; 1552-8618
• DOI: 10.1897/04-440R1.1

Heterocyclic 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 (beta-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 BNE 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 BNE 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.