Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
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DOI：
10.1016/j.tox.2009.06.006
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发表时间：
2009-08-21
期刊：
影响因子：
4.5
通讯作者：
Seralini, Gilles-Eric
中科院分区：
文献类型：
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作者：
Gasnier, Celine;Dumont, Coralie;Seralini, Gilles-Eric
草甘膦除草剂是世界上使用最广泛的除草剂;它们以不同的配方商业化。它们的残留物是环境中常见的污染物。此外，这些除草剂被散布在大多数食用的转基因植物上，这些转基因植物被改造成在其细胞中耐受高水平的这些化合物。在某些饲料中可接受高达400 ppm的残留物。我们将人肝HepG 2细胞（一种研究异生物质毒性的知名模型）暴露于四种不同的制剂和草甘膦，草甘膦通常在慢性体内调节研究中单独测试。我们用三种试验（Alcohol Blue（R）、MTT ToxiLight（R））测量细胞毒性，加上基因毒性（彗星试验）、抗雌激素作用（对ER α、ER β）和抗雄激素作用（对AR），使用基因报告测试。我们还通过芳香化酶活性和mRNA检查雄激素向雌激素的转化。在24小时内，所有制剂在亚农业剂量下的所有参数均被破坏。这些影响更多地取决于配方而不是草甘膦浓度。首先，我们观察到对于最具活性的制剂（11400），MDA-MB 453-kb 2细胞中的雄激素受体从0.5ppm开始的人细胞内分泌干扰，然后从2 ppm开始，HepG 2上两种雌激素受体的转录活性也被抑制。芳香化酶转录和活性从10 ppm开始被破坏。细胞毒性作用开始于10 ppm，采用Alcohol Blue测定法（最灵敏），DNA损伤在5 ppm。一个真实的细胞的影响，草甘膦除草剂残留在食品，饲料或在环境中，因此被认为是致癌物/诱变剂/生殖毒性的分类进行了讨论。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue (R), MTT ToxiLight (R)), plus genotoxicity (comet assay), anti-estrogenic (on ER alpha, ER beta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24 h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (11400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.