Aryl hydrocarbon receptor-mediated effects of chlorinated polycyclic aromatic hydrocarbons
Aryl hydrocarbon receptor-mediated effects of chlorinated polycyclic aromatic hydrocarbons
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DOI：
10.1021/tx700148b
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发表时间：
2007-09-01
影响因子：
4.1
通讯作者：
Shimoi, Kayoko
中科院分区：
文献类型：
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作者：
Ohura, Takeshi;Morita, Maki;Shimoi, Kayoko
氯代多环芳烃（CIPAHs）是一种普遍存在的环境污染物。然而，CIPAH的毒性仍不清楚。在这项研究中，芳基烃受体（AhR）介导的CIPAHs的活动进行了研究，通过使用酵母测定系统。所有与环境相关的18种CIPAH在测试中均显示出AhR活性;低分子量PAH（类似于三环和荧蒽衍生物）上的活性随氯原子数的增加而增加，但对于高分子量CIPAH（>四环）则不增加。在某些CIPAH诱导的MCF-7细胞中细胞色素P450 1A 1表达中也观察到类似的趋势。CIPAHs的AhR活性与溶剂可及表面积之间的构效关系呈抛物线关系，约350 A（2）/分子为与AhR结合的最佳配体尺寸。这些发现表明，CIPAH的空间维度显然影响其激活AhR的能力。最后，我们根据AhR活性讨论了CIPAH的毒性，估计其毒性约为二恶英的30-50倍。
Chlorinated polycyclic aromatic hydrocarbons (CIPAHs) with 3-5 rings are ubiquitous environmental contaminants. However, toxicities of CIPAHs remain unclear. In this study, aryl hydrocarbon receptor (AhR)-mediated activities of CIPAHs were investigated by using a yeast assay system. All environmentally relevant 18 CIPAHs showed the AhR activities in the test; the activities were elevated with the number of chlorine atoms on the lower molecular weight PAH (similar to three-ring and fluoranthene derivatives) but not for higher molecular weight CIPAHs (>four-ring). The similar trends were also observed in certain CIPAHs-induced cytochrome P450 1A1 expression in MCF-7 cells. The structure-activity relationship between the AhR activity and the corresponding solvent accessible surface area of CIPAHs revealed a parabolic relationship, with approximately 350 A (2)/molecule as the optimal dimensions as the ligand for binding to AhR. These findings indicate that the spatial dimensions of CIPAHs apparently influence their ability to activate the AhR. Finally, we discussed the toxicity of exposure to CIPAHs based on the AhR activities, estimated that it would be approximately 30-50 times higher than that of dioxins.