کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5560004 | 1403306 | 2017 | 13 صفحه PDF | دانلود رایگان |
- We evaluated the estrogenic potential of glyphosate-based herbicide constituents.
- Glyphosate but not other components present in 4 major commercial formulations activate ERα.
- Transcriptome profiles reflected proliferative effects, but did not overlap with that of an ERα gene expression biomarker.
- Molecular dynamics simulations show that glyphosate is unlikely to bind to ERα.
- Activation of ERα by glyphosate could be via a ligand-independent mechanism.
The safety, including the endocrine disruptive capability, of glyphosate-based herbicides (GBHs) is a matter of intense debate. We evaluated the estrogenic potential of glyphosate, commercial GBHs and polyethoxylated tallowamine adjuvants present as co-formulants in GBHs. Glyphosate (â¥10,000 μg/L or 59 μM) promoted proliferation of estrogen-dependent MCF-7 human breast cancer cells. Glyphosate also increased the expression of an estrogen response element-luciferase reporter gene (ERE-luc) in T47D-KBluc cells, which was blocked by the estrogen antagonist ICI 182,780. Commercial GBH formulations or their adjuvants alone did not exhibit estrogenic effects in either assay. Transcriptomics analysis of MCF-7 cells treated with glyphosate revealed changes in gene expression reflective of hormone-induced cell proliferation but did not overlap with an ERα gene expression biomarker. Calculation of glyphosate binding energy to ERα predicts a weak and unstable interaction (â4.10 kcal molâ1) compared to estradiol (â25.79 kcal molâ1), which suggests that activation of this receptor by glyphosate is via a ligand-independent mechanism. Induction of ERE-luc expression by the PKA signalling activator IBMX shows that ERE-luc is responsive to ligand-independent activation, suggesting a possible mechanism of glyphosate-mediated activation. Our study reveals that glyphosate, but not other components present in GBHs, can activate ERα in vitro, albeit at relatively high concentrations.
Journal: Food and Chemical Toxicology - Volume 108, Part A, October 2017, Pages 30-42