View : 1232 Download: 0
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, Seoyoung; Mun, Gil-im; Choi, Eun; Kim, Minjeong; Jeong, Ji Seong; Kang, Keon Wook; Jee, Sunha; Lim, Kyung-Min; Lee, Yun-Sil
- Ewha Authors
- 이윤실; 임경민; 김민정
- SCOPUS Author ID
- 이윤실; 임경민; 김민정
- Issue Date
- 2018
- Journal Title
- FOOD AND CHEMICAL TOXICOLOGY
- ISSN
- 0278-6915
1873-6351
- Citation
- FOOD AND CHEMICAL TOXICOLOGY vol. 111, pp. 125 - 132
- Keywords
- Bisphenol A; Cancer; Hepatic tumor; gamma H2AX; DNA damage; Proliferation
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 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.
- DOI
- 10.1016/j.fct.2017.11.010
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML