Evaluating the interactions of vertebrate receptors with persistent pollutants and antifouling pesticides using recombinant yeast assays
Evaluating the interactions of vertebrate receptors with persistent pollutants and antifouling pesticides using recombinant yeast assays
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DOI：
10.1007/s00216-006-0476-4
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发表时间：
2006-07-01
影响因子：
4.3
通讯作者：
Pina, Benjamin
中科院分区：
文献类型：
--
作者：
Noguerol, Tania-Noelia;Boronat, Susanna;Pina, Benjamin
开发用于筛选新化合物的潜在有害生物活性的体外方法是一种极其重要的方法，不仅可以提高其固有的环境安全性，而且可以提高公众对与其相关的安全标准的认识。在这项工作中，我们使用两种酵母系统来测试不同的化学物质结合和激活两种脊椎动物受体的能力，这两种受体与暴露动物群中污染的不良生物效应密切相关：雌激素受体（ER）和芳烃受体（AhR）。这里分析的一组化合物包括众所周知的污染物，如多氯联苯、pp '-滴滴涕和六氯苯，以及不太为人所知的新出现的假定污染物，如Sea-Nine、Irgarol和敌草隆。结果表明，这些化合物中的一些与一个或两个受体相互作用的能力，提供有关结构和活性之间的关系的提示，并建议在整个动物实验中已经描述的生物活性的机械解释。此外，我们表明，AhR可能有一个内在的配体混杂的ER，一个功能没有充分认识到在过去，由于在酵母为基础的检测与测试高度亲脂性物质的技术困难。
The development of in vitro methods for screening potentially harmful biological activities of new compounds is an extremely important way to increase not only their intrinsic environmental safety, but also the public perception of the safety standards associated with them. In this work we use two yeast systems to test the ability of different chemicals to bind and activate two vertebrate receptors which are intimately related to adverse biological effects of pollution in exposed fauna: the estrogen receptor (ER) and the aryl hydrocarbon receptor (AhR). The panel of compounds analysed here includes well-known pollutants, like PCBs, pp'-DDT and hexachlorobenzene, together with the less-known, emerging putative pollutants, such as Sea-Nine, Irgarol and diuron. Results show the ability of some of these compounds to interact with one or both receptors, provide hints about the relationship between structure and activity, and suggest mechanistic explanations for the biological activities already described in whole-animal experiments. In addition, we show that AhR may have an intrinsic ligand promiscuity comparable to that of ER, a feature not fully appreciated in the past due to the technical difficulties involved with testing highly lipophilic substances in yeast-based assays.