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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DOI：
10.2307/3432519
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发表时间：
1995-10-01
影响因子：
10.4
通讯作者：
SERRANO, FO
中科院分区：
文献类型：
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作者：
SOTO, AM;SONNENSCHEIN, C;SERRANO, FO
雌激素的定义是其诱导女性生殖道细胞增殖的能力。雌激素化合物的广泛化学多样性妨碍了根据化学结构准确预测雌激素活性。由于成本、复杂性和伦理问题，啮齿动物生物测定法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 测定的开发目的是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物质的雌激素性。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浓度的化学物质的情况下，通过类似接种 MCF-7 细胞获得的细胞数。在测试的化合物中，发现了几种“新”雌激素。通过 E-SCREEN 检测，烷基酚、邻苯二甲酸盐、一些 PCB 同系物和羟基化 PCB 以及杀虫剂狄氏剂、硫丹和毒杀芬具有雌激素作用。此外，这些化合物与雌二醇竞争与雌激素受体的结合，并增加 MCF-7 细胞中孕激素受体和 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）和胰岛素不会增加细胞产量。本文总结的工作目的是 a) 验证 E-SCREEN 测定； b) 筛查环境中存在的各种化学物质，以确定可能对野生动物和人类造成生殖影响的化学物质； c) 评估环境雌激素是否可能累积作用；最后 d) 讨论该测定法和其他测定法的可靠性，以在化学物质释放到环境中之前筛选其雌激素性。
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 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.