Influence of PCB153 on Oxidative DNA Damage and DNA Repair-related Gene Expression Induced by PBDE-47 in Human Neuroblastoma Cells in vitro.
 

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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.
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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.

Toxicol Sci. 2008 Oct 22;

Authors: Gao P, He P, Wang A, Xia T, Xu B, Xu Z, Niu Q, Guo L, Chen X

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 muM) and/or 5 muM PCB153 and 100 muM NAC (N-acetylcysteine) for 24 h. Results showed that reactive oxygen species (ROS) production in the 5 muM PBDE-47+PCB153 and 10 muM 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 muM PBDE-47, 5 muM PBDE-47+PCB153, and 10 muM PBDE-47+PCB153 groups compared to the control (P < 0.05). Furthermore, ROS formation and DNA strand breakage were dramatically increased in the 5 muM PBDE-47+PCB153 and 10 muM 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 muM 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 muM PBDE-47, 5 muM PBDE-47+PCB153, and 10 muM PBDE-47+PCB153 groups while X-ray repair cross-complementing gene 3 (Xrcc3) were significantly increased in the 10 muM PBDE-47 and 10 muM 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.

PMID: 18948301 [PubMed - as supplied by publisher]