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Environ Health Perspect. 2015 Dec;123(12):1271-9. doi: 10.1289/ehp.1409199. Epub 2015 May 1.

Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc.

Author information

1
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California, USA.

Abstract

BACKGROUND:

Humans are exposed to low-dose bisphenol A (BPA) through plastic consumer products and dental sealants containing BPA. Although a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies.

OBJECTIVE:

The objective of this study was to investigate the effect and the mechanism of low-dose BPA in mammary gland cells.

METHODS:

We evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA's effects.

RESULTS:

Low-dose BPA significantly promoted DNA damage, up-regulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells.

CONCLUSIONS:

Low-dose BPA exerted c-Myc-dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.

Comment in

PMID:
25933419
PMCID:
PMC4671234
DOI:
10.1289/ehp.1409199
[Indexed for MEDLINE]
Free PMC Article

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