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Toxicol Lett. 2010 Dec 15;199(3):261-8. doi: 10.1016/j.toxlet.2010.09.008. Epub 2010 Sep 22.

Loss of BRCA1 leads to an increased sensitivity to Bisphenol A.

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1
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. ljone010@umaryland.edu

Abstract

Humans are chronically exposed to the plasticizer, Bisphenol A (BPA), that can adversely affect the normal hormonal regulation of cellular functions by mimicking the actions of estrogen. This biological response to BPA may vary according to an individual's genetic characteristics (e.g., BRCA1 mutations or deletion). In this study, both cell culture and mouse models were used to elucidate whether the loss of BRCA1 function could affect BPA-mediated cell proliferation. In studies using BPA levels comparable to human exposures, we found that loss of BRCA1 enhances BPA-induced cell proliferation in both systems. In vitro, we found that loss of BRCA1 enhances BPA-induced ERα signaling. In vivo, we found that BPA administration stimulates mammary gland epithelial tissue/cell proliferation leading to hyperplasia in Brca1 mutant mice compared to wild-type control mice. These results suggest that the biological responses in BRCA1-deficient cells may depend on environmental exposures, specifically BPA.

PMID:
20868731
PMCID:
PMC3505996
DOI:
10.1016/j.toxlet.2010.09.008
[Indexed for MEDLINE]
Free PMC Article
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