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
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
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DOI：
10.1897/04-440r1.1
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发表时间：
2005-10-01
影响因子：
4.1
通讯作者：
Di Giulio, RT
中科院分区：
文献类型：
--
作者：
Wassenberg, DM;Nerlinger, AL;Di Giulio, RT
多环芳烃（PAHs）的杂环衍生物是环境污染物混合物的重要组成部分，但其对混合物毒性的影响尚不清楚。这些杂环通常共同存在于PAH混合物中，其中含有芳烃受体（AHR）的激动剂。这些研究的目的是探索两种PAH杂环，咔唑（CB）和二苯并噻吩（DBT），单独和与PAH型激动剂的AHR（β-萘酚酮[BNF]）对AHR介导的细胞色素P4501 A（CYP 1A）活性和鱼胚胎毒性的影响。胚胎的底heteroclitus暴露于CB或DBT，有和没有共同暴露于BNF咔唑单独轻微诱导，而DBT单独轻微降低，在卵内CYP 1A介导的乙氧基试卤灵-O-脱乙基酶（EROD）的活性相比，控制值。然而，暴露于CB或DBT减少卵EROD活性在胚胎共暴露于BNF咔唑和DBT的特点是在体外作为非竞争性CYP 1A抑制剂。咔唑和DBT增强了BNF的胚胎毒性，尽管这两种化合物本身都没有胚胎毒性。在污染的生态系统中，CB和DBT与PAH型AHR诱导剂的共存可能会增加PAH型AHR激动剂在这些环境中的毒性，在估计PAH混合物的胚胎毒性时可能需要考虑。
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 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.