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Food Chem Toxicol. 2017 Oct;108(Pt A):30-42. doi: 10.1016/j.fct.2017.07.025. Epub 2017 Jul 12.

Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.

Author information

1
Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
2
Genomics Centre, King's College London, Waterloo Campus, 150 Stamford Street, London SE1 9NH, United Kingdom.
3
Integrated Systems Toxicology Division, US Environmental Protection Agency, 109 T.W. Alexander Dr MD-B143-06, Research Triangle Park, NC 27711, United States.
4
Instituto de Ciencias Químicas, Facultad de Ciencias, Universidad Austral de Chile, Independencia 641, Valdivia, Chile.
5
Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom. Electronic address: michael.antoniou@kcl.ac.uk.

Abstract

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 (≥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 (-4.10 kcal mol-1) compared to estradiol (-25.79 kcal mol-1), 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.

KEYWORDS:

Breast cancer; Endocrine disrupting effects; Estrogen receptor; Glyphosate; Pesticides

PMID:
28711546
DOI:
10.1016/j.fct.2017.07.025
[Indexed for MEDLINE]
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