An evaluation on combination effects of phenolic endocrine disruptors by estrogen receptor binding assay
An evaluation on combination effects of phenolic endocrine disruptors by estrogen receptor binding assay
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雌激素受体结合试验评价酚类内分泌干扰物的联合作用
DOI：
10.1016/j.tiv.2012.05.017
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发表时间：
2012-09-01
影响因子：
3.2
通讯作者：
Li, Jiangling
中科院分区：
文献类型：
--
作者：
Li, Zhengyan;Zhang, Haili;Li, Jiangling
酚类化合物广泛分布于自然环境中，通常以每升纳摩尔或微摩尔的混合物形式存在。在酚类化合物中，4-壬基酚、4-t-辛基酚、双酚A和2,4-二氯酚因其在自然环境中的丰度和危险性而备受关注。前三种物质被认为是内分泌干扰物，在各种生物体中引起女性化，而后者的雌激素作用需要进一步澄清。本研究旨在以雌激素受体结合为终点，评价这些化学物质的联合作用。采用基于ELISA的受体结合法，避免了传统检测方法的放射性污染。结果表明，这些化学物质均能与雌激素受体结合，并具有双酚a > 4-t-辛基酚> 4-壬基酚> 2,4-二氯酚的相对结合亲和力。将四种化学物质以等效比和等环境水平比两种方式混合，并采用毒性单位法和浓度相加模型评价其对受体结合的组合效应。这两种混合物的结果都显示出拮抗模式，这被认为是雌激素受体结合试验的一般作用模式，因为受体上的配体结合是竞争性的。(C) 2012 Elsevier Ltd.版权所有。
Phenolic compounds are widely distributed in the natural environment, typically existing as a mixture at the nanomole or micromole per liter level. Among the phenolic compounds, 4-nonylphenol, 4-t-octylphenol, bisphenol A and 2,4-dichlorophenol attract the most concern due to their abundance and risks in the natural environment. The former three are known as endocrine disruptors causing feminization in various organisms, whereas the latter requires further clarification for its estrogenic effect. This study aims to evaluate the combination effects of these chemicals with estrogen receptor binding as an endpoint. An ELISA based receptor binding assay was employed to avoid radioactive pollution in the traditional assay. The results showed that all these chemicals could bind with estrogen receptor with a relative binding affinity of bisphenol A > 4-t-octylphenol > 4-nonylphenol > 2,4-dichlorophenol. The four chemicals were further mixed in two ways, at an equipotent ratio and at an equal environmental level ratio, and their combination effects on receptor binding were evaluated with both the toxicity units method and concentration addition model. The resulting effects of both mixtures showed an antagonistic mode, which was assumed to be a general mode of action with estrogen receptor binding assay due to competitive ligand binding on receptors. (C) 2012 Elsevier Ltd. All rights reserved.