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.

Citation: Pfeifer D, Chung YM, Hu MC. 2015. Effects of low-dose bisphenol A on DNA damage and proliferation of breast cells: the role of c-Myc. Environ Health Perspect 123:1271–1279; http://dx.doi.org/10.1289/ehp.1409199

*These authors contributed equally to this work.

Address correspondence to M.C-T. Hu, Division of Gynecologic Oncology, Stanford University School of Medicine, 300 Pasteur Dr. HG332, Stanford, CA 94305-5317 USA. Telephone: (650) 721-2056. E-mail: mhu1@stanford.edu

This work was supported by the Avon Foundation for Women (grants 02-2010-063 and 02-2013-051), and by the National Institutes of Health (grant CA113859 to M.C-T.H.).

The authors declare they have no actual or potential competing financial interests.

Received: 10 September 2014 Accepted: 28 April 2015 Advance Publication: 1 May 2015 Final Publication: 1 December 2015

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