Low-dose environmental endocrine disruptors, increase aromatase activity, estradiol biosynthesis and cell proliferation in human breast cells

Molecular and Cellular Endocrinology
Graeme P Williams, Philippa D Darbre

Abstract

Phenolic endocrine-disrupting compounds (EDCs) have long been suspected of increasing human breast cancer risk, via aromatase up-regulation; however, the metabolic effects upon aromatase in human breast cells exposed to environmentally relevant concentrations of phenolic compounds, have not been addressed. To examine the mechanistic responses of aromatase CYP19A1 mRNA, aromatase activity, estradiol biosynthesis and cellular proliferation, in three human breast cell lines, exposed to seven phenolic compounds, at environmentally relevant concentrations. MCF-7 and ZR-75-1 breast cancer cells, and HMF3A breast fibroblasts were treated with specific concentrations of p,p'-DDT, methoxychlor, benzophenone-2, bisphenol A, bisphenol S, 4-phenylphenol and n-butylparaben, with and without the presence of aromatase inhibitors and estrogen receptor inhibitors. All test EDCs up-regulated aromatase mRNA, increased aromatase activity, significantly increased the aromatase-induced biosynthesis of the breast carcinogen 17β-estradiol, and increased ERα-positive breast cell proliferation. Inadvertent exposures to 'phenolic' EDCs, increase estradiol biosynthesis, and estrogen-sensitive breast cancer proliferation.

Citations

Jul 29, 2020·Birth Defects Research·Philippa D Darbre
Aug 5, 2020·Journal of Neuroendocrinology·Pascal CoumailleauThierry D Charlier
Dec 18, 2020·Frontiers in Nutrition·Barbara J StillwaterOrnella I Selmin
Nov 9, 2020·Environmental Toxicology and Pharmacology·Ayse Basak Engin, Atilla Engin
Aug 10, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Marie Alfrede MvondoSylvie Léa Wansi Ngnokam
Jan 9, 2022·BMC Women's Health·Anna Merklinger-GruchalaMaria Kapiszewska

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