Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc.
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.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California, USA.
Daniella
D
Pfeifer
Young Min
YM
Chung
Mickey C-T
MC
Hu
D001559:Benzhydryl Compounds / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D016259:Genes, myc; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D010636:Phenols; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C006780:bisphenol A; D000098826:Bisphenol A Compounds