A Ternary Mixture of Common Chemicals Perturbs Benign Human Breast Epithelial Cells More Than the Same Chemicals Do Individually.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Shanaz H DairkeeWilliam H Goodson

Abstract

As a continuous source of hormonal stimulation, environmentally ubiquitous estrogenic chemicals, ie, xenoestrogens (XEs), are a potential risk factor for breast carcinogenesis. Given their wide distribution in the environment and the fact that bisphenol-A (BPA), methylparaben (MP), and perfluorooctanoic acid (PFOA) are uniformly detected in unselected body fluid samples, it must be assumed that humans are simultaneously exposed to these chemicals almost daily. We studied the effects of a ternary mixture of BPA, MP, and PFOA on benign breast epithelial cells at the range of concentrations observed for single chemicals in human samples. Measurements of exposure impact relevant to the breast were based on endpoints associated with "hallmarks" of cancer and "key characteristics" of carcinogens. These included modulation of total estrogen receptor (ER)α, phosphorylated ERα (pERα), total ERβ, S-phase induction, and apoptotic evasion. Data from live cell measurements were fit to a log-linear dose-response model. Concentration-dependent reduction of ERβ and apoptosis evasion was observed concurrently with the induction of ERα, pERα, and S-phase fraction, and an increased rate of cell proliferation. Beyond additive effects predicted by ...Continue Reading

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Citations

Aug 25, 2020·Reviews on Environmental Health·William H GoodsonDavid O Carpenter
Mar 8, 2020·International Journal of Environmental Research and Public Health·Alexis M TemkinLisa M Kamendulis
Mar 11, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Martyn T SmithMark Fielden
Sep 7, 2020·Pharmacology & Therapeutics·Anna FishbeinDipak Panigrahy
Jan 21, 2020·European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·Robyn ReddingtonYazan Masannat

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorting
FACS
chemical treatment
xenograft

Software Mentioned

Stata
CellQuest
Excel

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