ToxSci Advance Access published online on October 22, 2008
Toxicological Sciences, 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
For Correspondence: Prof. AiGuo Wang and Prof. XueMin Chen, Department of Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, People's Republic of China, Tel: 86-27-83692715, Fax: 86-27-83692701, Email: wangaiguo{at}mails.tjmu.edu.cn and cxm3636{at}yahoo.com.cn
Received August 11, 2008; revision received October 9, 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, 10 µM) and/or 5 µM PCB153 and 100 µM NAC (N-acetylcysteine) for 24 h. Results showed that reactive oxygen species (ROS) production in the 5 µM PBDE-47+PCB153 and 10 µM 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 10 µM PBDE-47, 5 µM PBDE-47+PCB153, and 10 µM PBDE-47+PCB153 groups compared to the control (P < 0.05). Furthermore, ROS formation and DNA strand breakage were dramatically increased in the 5 µM PBDE-47+PCB153 and 10 µM PBDE-47+PCB153 groups compared to the corresponding PBDE-47 only group and the PCB153 group (P < 0.05). The level of 8-OHdG was significantly increased in the 10 µM PBDE-47+PCB153 group compared to the corresponding PBDE-47 only group and the PCB153 group (P < 0.05). The PBDE-47 group co-incubated 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 10 µM PBDE-47, 5 µM PBDE-47+PCB153, and 10 µM PBDE-47+PCB153 groups while X-ray repair cross-complementing gene 3 (Xrcc3) were significantly increased in the 10 µM PBDE-47 and 10 µM PBDE-47+PCB153 groups compared to the control (P < 0.05). The PBDE-47 groups co-incubated 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.