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Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo

Title
Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo
Authors
Kim S.Mun G.-I.Choi E.Kim M.Jeong J.S.Kang K.W.Jee S.Lim K.-M.Lee Y.-S.
Ewha Authors
임경민김민정
SCOPUS Author ID
임경민scopus
Issue Date
2018
Journal Title
Food and Chemical Toxicology
ISSN
0278-6915JCR Link
Citation
vol. 111, pp. 125 - 132
Keywords
Bisphenol ACancerDNA damageHepatic tumorProliferationγH2AX
Publisher
Elsevier Ltd
Indexed
SCI; SCIE; SCOPUS scopus
Abstract
An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins. At concentrations higher than 10 μM, these effects disappeared, reflecting a non-monotonic dose-response relationship. Notably, histone H2AX was activated following exposure to BPA, which is a sensitive marker of DNA damage. Importantly, proliferative foci and DNA damage were also observed in liver tissue of rats orally exposed to BPA at 0.5 mg/kg for 90 days, from juvenile age (postnatal day 9) through adulthood. Reactive oxygen species appeared to play a role in the BPA-induced proliferation and DNA damage, as evidenced by a partial reversal of both processes upon pretreatment with an antioxidant, N-acetylcysteine. Collectively, these results demonstrate that submicromolar BPA concentrations induce the DNA damage and promote the cell proliferation in the liver, which may support its role as a risk factor for hepatocarcinogenicity. © 2017 Elsevier Ltd
DOI
10.1016/j.fct.2017.11.010
Appears in Collections:
약학대학 > 약학과 > Journal papers
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