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PMID: 25933419 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Environmental health perspectives ·Vol. 123 ·No. 12 ·2015-12-00 ·Pages 1271-9

Pfeifer D, Chung YM, Hu MC

Abstract

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

MeSH Terms
Benzhydryl Compounds/toxicity Cell Line Cell Line, Tumor Cell Proliferation/drug effects DNA Damage/drug effects Environmental Pollutants/toxicity Estrogen Receptor alpha/metabolism Female Gene Silencing Genes, myc Humans Mammary Glands, Human/cytology,drug effects,metabolism Phenols/toxicity Proto-Oncogene Proteins c-myc/genetics,metabolism RNA, Small Interfering/genetics Up-Regulation
Chemicals
Benzhydryl Compounds Environmental Pollutants Estrogen Receptor alpha Phenols Proto-Oncogene Proteins c-myc RNA, Small Interfering bisphenol A
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pfeifer Daniella
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California, USA.
Chung Young Min
Hu Mickey C-T
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Article Info
Journal
Environmental health perspectives
Abbr.
Environ Health Perspect
ISSN
1552-9924
DOI
10.1289/ehp.1409199
Published
2015-12-00
Epub
2015-00-01
Pages
1271-9
Language
English
Region
United States
NLM ID
0330411
PMCID
PMC4671234
Subset
IM
Grants
NCI NIH HHS · R01 CA113859 · United States
NCI NIH HHS · CA113859 · United States
Corrections
CommentIn
PMID: 26623713
External Links
PubMed source DOI: 10.1289/ehp.1409199 PMC Full Text View journal details
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