ToxSci Advance Access originally published online on October 22, 2008
Toxicological Sciences 2009 107(1):165-170; doi:10.1093/toxsci/kfn224
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Influence of PCB153 on Oxidative DNA Damage and DNA Repair–Related Gene Expression Induced by PBDE-47 in Human Neuroblastoma Cells In Vitro
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China
1 To whom correspondence should be addressed at Department of Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, China. Fax: +86-27-83692701. E-mail: wangaiguo{at}mails.tjmu.edu.cn; cxm3636{at}yahoo.com.cn.
Received August 11, 2008; accepted October 9, 2008
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Abstract |
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We studied the relationship between 2,2,4,4-tetrabromodiphenyl ether (PBDE-47) and oxidative DNA damage as well as the mode of interaction between PBDE-47 and 2,2,4,4,5,5-hexachlorobiphenyl (PCB153) by incubating SH-SY5Y cells in four doses of PBDE-47 (0, 1, 5, 10µM) and/or 5µM PCB153 and 100µM NAC (N-acetylcysteine) for 24 h. Results showed that reactive oxygen species (ROS) production in the 5µM PBDE-47 + PCB153 and 10µM PBDE-47 + PCB153 groups were significantly higher than that of the control group (p < 0.05). DNA strand breakage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were significantly increased in the 10µM PBDE-47, 5µM PBDE-47 + PCB153, and 10µM PBDE-47 + PCB153 groups compared with the control (p < 0.05). Furthermore, ROS formation and DNA strand breakage were dramatically increased in the 5µM PBDE-47 + PCB153 and 10µM PBDE-47 + PCB153 groups compared with the corresponding PBDE-47 only group and the PCB153 group (p< 0.05). The level of 8-OHdG was significantly increased in the 10µM PBDE-47 + PCB153 group compared with the corresponding PBDE-47 only group and the PCB153 group (p < 0.05). The PBDE-47 group coincubated with NAC decreased the ROS level and ameliorated PBDE-47–mediated DNA damage. The mRNA expression levels of X-ray repair cross-complementing gene 1 (Xrcc1) were significantly decreased in the 10µM PBDE-47, 5µM PBDE-47 + PCB153, and 10µM PBDE-47 + PCB153 groups, whereas X-ray repair cross-complementing gene 3 (Xrcc3) were significantly increased in the 10µM PBDE-47 and 10µM PBDE-47 + PCB153 groups compared with the control (p < 0.05). The PBDE-47 groups coincubated with NAC, however, considerably increased Xrcc1 while decreasing Xrcc3 mRNA expression (p < 0.05). These results indicate that PBDE-47 induced oxidative DNA damage and that PBDE-47 combined with PCB153 may increase such effects in SH-SY5Y cells in vitro. Furthermore, our results suggest that oxidative stress is responsible for DNA damage induced by PBDE-47.
Key Words: PBDE-47; PCB153; oxidative stress; DNA Damage; 8-OHdG; DNA repair–related gene.