Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo
- 주제(키워드) Bisphenol A , Cancer , Hepatic tumor , gamma H2AX , DNA damage , Proliferation
- 주제(기타) Food Science & Technology; Toxicology
- 설명문(일반) [Kim, Seoyoung; Mun, Gil-im; Choi, Eun; Kim, Minjeong; Lim, Kyung-Min; Lee, Yun-Sil] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Jeong, Ji Seong] Korea Inst Toxicol, Dev & Reprod Toxicol Res Grp, Daejeon 34114, South Korea; [Kang, Keon Wook] Seoul Natl Univ, Coll Pharm, Dept Pharm, Seoul 08826, South Korea; [Kang, Keon Wook] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul 08826, South Korea; [Jee, Sunha] Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 03722, South Korea; [Jee, Sunha] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 PERGAMON-ELSEVIER SCIENCE LTD
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000150046
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.fct.2017.11.010
초록/요약
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 mu M, 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 SPA 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.
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