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-tetrabromodiphenylether (PBDE-47) and oxidative DNA damage as well as the modeof 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 100µMNAC (N-acetylcysteine) for 24 h. Results showed that reactiveoxygen species (ROS) production in the 5µM PBDE-47 + PCB153and 10µM PBDE-47 + PCB153 groups were significantly higherthan that of the control group (p < 0.05). DNA strand breakageand 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were significantlyincreased 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 breakagewere dramatically increased in the 5µM PBDE-47 + PCB153and 10µM PBDE-47 + PCB153 groups compared with the correspondingPBDE-47 only group and the PCB153 group (p< 0.05). The levelof 8-OHdG was significantly increased in the 10µM PBDE-47+ PCB153 group compared with the corresponding PBDE-47 onlygroup and the PCB153 group (p < 0.05). The PBDE-47 groupcoincubated with NAC decreased the ROS level and amelioratedPBDE-47–mediated DNA damage. The mRNA expression levelsof X-ray repair cross-complementing gene 1 (Xrcc1) were significantlydecreased in the 10µM PBDE-47, 5µM PBDE-47 + PCB153,and 10µM PBDE-47 + PCB153 groups, whereas X-ray repaircross-complementing gene 3 (Xrcc3) were significantly increasedin the 10µM PBDE-47 and 10µM PBDE-47 + PCB153 groupscompared with the control (p < 0.05). The PBDE-47 groupscoincubated with NAC, however, considerably increased Xrcc1while decreasing Xrcc3 mRNA expression (p < 0.05). Theseresults indicate that PBDE-47 induced oxidative DNA damage andthat PBDE-47 combined with PCB153 may increase such effectsin SH-SY5Y cells in vitro. Furthermore, our results suggestthat oxidative stress is responsible for DNA damage inducedby PBDE-47.