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首页> 外文期刊>Life sciences >Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines.
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Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines.

机译：报告细胞系中持久性杀虫剂激活α和β雌激素受体。

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摘要

Many persistent pesticides have been implicated in reproductive and developmental adverse effects, in man and wildlife. It has been hypothesized that these so-called xeno-hormones could upset the endocrine system function by binding to human estrogen receptor alpha and beta (ERalpha, beta) and thus be responsible for the higher incidence of breast and cervical cancer, infertility and endometriosis. In this report, forty-nine pesticides were tested for ERalpha and beta activation or inhibition in stable reporter cell lines, HELN ERalpha and ERbeta. Stable transfection of the ERalpha and ERbeta constructs together with an estrogen reporter luciferase vector into the HeLa cell line resulted in two estradiol-sensitive cell lines. In our model, fifteen of the tested pesticides were found to agonize the ERalpha-mediated transcription in a dose-dependent manner and DDT, trans-nonachlor, chlordane, fenvalerate and toxaphene were also capable to activate ERbeta. Antagonistic activities toward hERalpha and hERbeta were shown in three (carbaryl, pentachlorophenol and 2,4,5-trichlorophenoxyacetic acid) and seven (chlordecone, methoxychlor, carbaryl, endosulfan, endrin, dieldrin, aldrin) pesticides, respectively. Remarkably chlordecone and methoxychlor which were the most effective antagonist compounds for hERbeta, were agonists for hERalpha. Although the ERalpha activation potential of the pesticides was lower than that of estradiol, the overall body scale response might be amplified by the ability of pesticides to act via several mechanisms and by frequent and prolonged exposure to different pesticides, even at low concentrations.
机译：许多持久性农药与人类和野生动植物的生殖和发育有关。据推测，这些所谓的异种激素可通过与人雌激素受体α和β（ERα，β）结合而破坏内分泌系统的功能，从而导致乳腺癌和宫颈癌，不孕症和子宫内膜异位症的发病率升高。在此报告中，测试了49种农药在稳定的报告细胞系HELN ERalpha和ERbeta中对ERalpha和beta的激活或抑制。 ERalpha和ERbeta构建体与雌激素报告荧光素酶载体的稳定转染到HeLa细胞系中产生了两种雌二醇敏感性细胞系。在我们的模型中，发现有15种受测试的农药以剂量依赖的方式激动ERalpha介导的转录，而滴滴涕，反式六氯丹，氯丹，苯丙戊酸盐和毒杀芬也能够激活ERbeta。分别对三种农药（甲萘威，五氯苯酚和2,4,5-三氯苯氧基乙酸）和七种农药（十氯酮，甲氧氯，甲氧萘威，硫丹，异狄氏剂，狄氏剂，艾氏剂）显示出对hERalpha和hERβ的拮抗活性。十氯酮和甲氧基氯是hERbeta的最有效拮抗剂，它们是hERalpha的激动剂。尽管农药的ERalpha活化潜能低于雌二醇，但通过多种机制发挥作用的能力以及频繁长期接触不同农药（即使在低浓度下）也可能会放大人体的整体规模反应。

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