The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.
The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.
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电子屏幕测定作为识别雌激素的工具：雌激素环境污染物的更新。
DOI：
10.1289/ehp.95103s7113
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发表时间：
1995-10
影响因子：
10.4
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中科院分区：
文献类型：
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雌激素的定义是它们诱导女性生殖道细胞增殖的能力。雌激素化合物的广泛的化学多样性排除了基于化学结构的雌激素活性的准确预测。啮齿动物生物测定法由于其成本、复杂性和伦理问题，不适合在化学品释放到环境中之前对其进行大规模筛选。E-SCREEN测定法被开发用于使用雌激素对其靶细胞的增殖作用作为终点来评估环境化学品的雌激素性。该定量测定比较了在不存在雌激素（阴性对照）和存在17 β-雌二醇（阳性对照）以及一系列疑似雌激素的化学物质浓度的情况下，通过类似的MCF-7细胞接种获得的细胞数。在测试的化合物中，发现了几种“新”雌激素; E-SCREEN检测显示，烷基酚、邻苯二甲酸酯、一些多氯联苯同系物和羟基化多氯联苯，以及杀虫剂狄氏剂、硫丹和毒杀芬具有雌激素活性。此外，这些化合物与雌二醇竞争结合雌激素受体，并增加MCF-7细胞中孕酮受体和pS2的水平，正如雌激素模拟物所预期的那样。重组人生长因子（bFGF，EGF，IGF-1）和胰岛素没有增加细胞产量。本文概述的工作目的是：a）验证E-SCREEN测定法; B）筛选环境中存在的各种化学品，以确定可能对野生动物和人类生殖产生影响的化学品; c）评估环境雌激素是否可能累积作用;最后，d）讨论在化学品释放到环境中之前对其进行雌激素活性筛选的这种和其他分析方法的可靠性。
Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several "new" estrogens were found; alkylphenols, phthalates, some PCB congeners and hydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxaphene were estrogenic by the E-SCREEN assay. In addition, these compounds competed with estradiol for binding to the estrogen receptor and increased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF, EGF, IGF-1) and insulin did not increase in cell yields. The aims of the work summarized in this paper were a) to validate the E-SCREEN assay; b) to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulatively; and finally d) to discuss the reliability of this and other assays to screen chemicals for their estrogenicity before they are released into the environment.