Influence of PCB153 on oxidative DNA damage and DNA repair-related gene expression induced by PBDE-47 in human neuroblastoma cells in vitro.

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