Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts.
Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts.
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DOI：
10.1002/etc.581
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发表时间：
2011-08
影响因子：
4.1
通讯作者：
Denison, Michael S.
中科院分区：
文献类型：
--
作者：
He, Guochun;Zhao, Bin;Denison, Michael S.
橡胶轮胎材料的渗滤液含有一种复杂的化学物质混合物，以前曾显示对水生生物产生毒性和生物效应。虽然这些渗滤液在鱼类中诱导AhR受体（AhR）依赖性细胞色素P4501A1表达的能力表明存在AhR活性化学物质，但没有研究负责化学物质及其与AhR信号通路的直接相互作用。通过结合AhR为基础的生物测定，我们证明了轮胎提取物刺激AhR DNA结合和AhR依赖基因表达的能力，并证实了相关化学物质具有代谢不稳定性。应用CALUX （Chemical-Activated LUciferase gene eXpression）细胞生物检测技术进行毒性鉴定评价，不仅发现轮胎提取物中含有多种已知的AhR活性多环芳烃，还鉴定出2-甲基噻唑苯并噻唑和2-巯基苯并噻唑为AhR激动剂。通过对一系列结构多样的苯并噻唑类药物的分析，发现了许多可以直接刺激AhR DNA结合并瞬时激活AhR信号通路的药物，并确定了苯并噻唑类药物是一类新的AhR激动剂。除了这些化合物外，大量部分的AhR激动剂活性相对较高，这强烈表明轮胎提取物中含有大量物理化学上不同的AhR激动剂，其特性和毒理学/生物学意义尚不清楚。
Leachate from rubber tire material contains a complex mixture of chemicals previously shown to produce toxic and biological effects in aquatic organisms. While the ability of these leachates to induce Ah receptor (AhR)-dependent cytochrome P4501A1 expression in fish indicated the presence of AhR active chemicals, the responsible chemical(s) and their direct interaction with the AhR signaling pathway were not examined. Using a combination of AhR-based bioassays, we have demonstrated the ability of tire extract to stimulate both AhR DNA binding and AhR-dependent gene expression and confirmed that the responsible chemical(s) was metabolically labile. The application of CALUX (Chemical-Activated LUciferase gene eXpression) cell bioassay-driven toxicant identification evaluation not only revealed that tire extract contained a variety of known AhR-active polycyclic aromatic hydrocarbons, but also identified 2-methylthiobenzothiazole and 2-mercaptobenzothiazole as AhR agonists. Analysis of a structurally diverse series of benzothiazoles identified many that could directly stimulate AhR DNA binding and transiently activate the AhR signaling pathway and identified benzothiazoles as a new class of AhR agonists. In addition to these compounds, the relatively high AhR agonist activity of a large number of fractions strongly suggests that tire extract contains a large number of physiochemically diverse AhR agonists whose identities and toxicological/biological significances are unknown.
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影响因子：
11.8
作者：
Mantecca, Paride;Gualtieri, Maurizio;Camatini, Marina
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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