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

REACTIVE oxygen species; BIOLOGICAL assay; BREAST; CELL culture; CELL cycle; CELL physiology; DENTAL resins; DNA; FLUORESCENT antibody technique; GENETIC techniques; ONCOGENES; PHENOLS; RESEARCH funding; T-test (Statistics); WESTERN immunoblotting; DATA analysis software; DESCRIPTIVE statistics

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 immuno-fluorescence 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. [ABSTRACT FROM AUTHOR]

Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)