期刊
TOXICOLOGY
卷 262, 期 3, 页码 184-191出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2009.06.006
关键词
Glyphosate; Roundup; Endocrine disruptor; HepG2; Sexual steroids
资金
- Conseil Regional de Basse-Normandie
- CRIIGEN (Committee for Independent Research and Information on Genetic Engineering)
- Ethic Committee of U a Nature Group/Jardin Bio
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.
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