Binding of polycyclic aromatic hydrocarbons (PAHs) to teleost aryl hydrocarbon receptors (AHRs)
Binding of polycyclic aromatic hydrocarbons (PAHs) to teleost aryl hydrocarbon receptors (AHRs)
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DOI：
10.1016/s1096-4959(02)00105-7
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发表时间：
2002-09-01
影响因子：
2.2
通讯作者：
Hodson, PV
中科院分区：
文献类型：
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作者：
Billiard, SM;Hahn, ME;Hodson, PV
多环芳烃（PAHs）是一种普遍存在的环境污染物，对鱼类种群构成潜在风险。现场和实验室研究均表明，鱼类在生命早期阶段暴露于多环芳烃可模拟平面卤化烃（PHH）的胚胎毒性效应，其中最强的是2，3，7，8-四氯二苯并-对-二恶英。PHH毒性由芳香烃受体（AHR）介导，PHH效力由其AHR结合亲和力和CYP 1A诱导效力预测。然而，AHR的作用，如果有的话，在介导的多环芳烃对鱼类的发育影响仍然未知。在这项研究中，我们研究了一组PAH的AHR结合亲和力，这些PAH先前已根据其诱导硬骨鱼CYP 1A的效力进行了排名。诱导CYP 1A的PAH抑制[3 H]TCDD与体外表达的虹鳟鱼AHR和PLHC-1鱼肝癌细胞AHR的结合。通常，AHR结合亲和力的相对排序预测了其他研究中报告的这些相同PAH诱导CYP 1A的排序。在整个幼鳟鱼和RTL-W1细胞中，与PLHC-1 AHR（刺激）的结合与CYP 1A诱导（反应）的EC 50之间存在强烈的正相关关系，但EC 50远高于1：1刺激/反应关系的预期值。这些数据表明，PAH与硬骨鱼AHR结合的能力可预测PAH诱导CYP 1A的效力。如果多环芳烃毒性是受体介导的，并通过诱导效力预测，我们将有一个强大的机制为基础的工具，快速评估风险的毒性鱼类的多环芳烃从任何来源。(C)2002年爱思唯尔科学公司All rights reserved.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, environmental contaminants that pose a potential risk to fish populations. Both field and laboratory studies suggest that exposure of the early life stages of fish to PAH can mimic the embryotoxic effects of the planar halogenated hydrocarbons (PHHs), the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin. PHH toxicity is mediated by the aryl hydrocarbon receptor (AHR) and PHH potency is predicted by its AHR-binding affinity and CYP1A induction potency. However, the role of the AHR, if any, in mediating the developmental effects of PAH to fish remains unknown. In this study we looked at the AHR binding affinity of a test set of PAH that had been previously ranked for their potency for inducing teleost CYP1A. PAH that induced CYP1A inhibited [3 H]TCDD binding to in vitro-expressed AHRs from rainbow trout and the AHR expressed in PLHC-1 fish hepatoma cells. Generally, the relative rank order for AHR binding affinity predicted the rank order of these same PAH for inducing CYP1A reported in other studies. There was a strong, positive relationship between binding to the PLHC-1 AHR (stimulus) and the EC50s for CYP1A induction (response) in whole juvenile trout and in RTL-W1 cells, but EC50s were much higher than expected for a 1:1 stimulus/response relationship. These data show that the ability of PAH to bind to teleost AHR predicts PAH potency for CYP1A induction. If PAH toxicity is receptor-mediated and predicted by induction potencies, we will have a powerful mechanistic-based tool for rapidly assessing the risk of toxicity to fish of PAH from any source. (C) 2002 Elsevier Science Inc. All rights reserved.