SCIENCE: Even Low levels of BPA are Toxic to Cells
Published 14 Dec 2015
A new study published in Environmental Health Perspectives (1) this month has shown that low, environmentally relevant doses of Bisphenol A (BPA) can cause DNA damage and proliferation of breast cells, regardless of their oestrogen receptor status. The authors also report that levels of a cancer-promoting protein, c-Myc, increased in response to low-dose BPA exposure, suggesting a possible mechanism of action for BPA to induce breast cancer.
Bisphenol A is found in household plastics, till receipts and dental fillings. It is ubiquitous in the environment and routinely detected in human body fluids and tissues (2). It is a known oestrogen mimic, which induces proliferation of oestrogen receptor α (ERα)-positive breast tumour cells (3). Furthermore, BPA exposure increases mammary cancers in rodents (3) and may increase breast cancer risk in humans. Previous cell culture studies have shown high concentrations of BPA are toxic to cells and cause DNA damage, but these effects have not been seen previously following exposure to low, environmentally relevant, concentrations. This may be because the earlier studies exposed breast cells to BPA for shorter time periods (up to 24hr, as opposed to 72hr).
The current study found that low-dose exposure of BPA to human breast cells grown in 3D tissue culture generated higher levels of DNA-damaging reactive oxygen species; more DNA damage, an increased production of cell-cycle regulatory proteins, including the cancer promoting protein c-Myc; and induced proliferation of breast cells, including ERα-positive and ERα-negative breast cancer cells and normal ERα-negative breast cells. The authors used a molecular biology technique (RNA silencing) to switch off expression of c-Myc; BPA-induced cellular events no longer occurred, suggesting that c-Myc is essential for regulating the effects of BPA on DNA damage and proliferation in breast cells.
This is the first study to show that low-dose BPA increases the production of c-Myc, which induces DNA damage and proliferation in ERα-negative breast cells. This demonstrates that BPA can act on breast cells through ERα-independent mechanisms, which suggests that it might have effects on other tissues.
The findings provide significant evidence of the adverse effects of low-dose BPA on human breast cells and propose a mechanism for these effects. Breast Cancer UK has long campaigned for BPA to be banned due to its potential role in increasing breast cancer risk.
For further details on BPA and breast cancer see our fact sheet.
1. Pfeifer D. et al. (2015). Effects of low-dose bisphenol A on DNA damage and proliferation of breast cells: the role of c-Myc. Environmental Health Perspectives 123:1271–1279. http://dx.doi.org/10.1289/ehp.1409199
2 Vandenberg L.N. et al. (2010). Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A. Environmental Health Perspectives 118 (8) 1055-1070. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920080/
3 Jenkins S. et al. (2012). Endocrine-active chemicals in mammary cancer causation and prevention. Journal of Steroid Biochemistry and Molecular Biology. 129(3-5): 191-200. http://www.ncbi.nlm.nih.gov/pubmed/21729753