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

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-? (ER?)-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 ER?-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.

SUBMITTER: Pfeifer D 

PROVIDER: S-EPMC4671234 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature