Gao Ping, He Weihong, He Ping, Xu Bayi
Department of Occupational and 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, China.
Wei Sheng Yan Jiu. 2008 Sep;37(5):525-8.
To explore the effects of PCB153 on DNA damage and DNA repair-related gene expressions induced by PBDE-47 in SH-SY5Y cells.
SH-SY5Y cells were incubated with different concentrations of 1,5 and 10 micromol/L PBDE-47 or/and 5 micromol/L PCB153 and antioxidant n-acetyl cysteine (NAC 100 micromol/L) for 24h in vitro, percentage of DNA in the tail, olive tail moment, the mRNA expression levels of XRCC1 and XRCC3 were measured respectively.
PBDE-47 increased percentage of DNA in the tail and olive tail moment significantly at doses of 5 micromol/L and above in a concentration-dependent manner compared to the control (P < 0.05). The percentage of DNA in the tail and olive tail moment were significantly higher in cells treated by 5 micromol/L PBDE-47 + 5 micromol/L PCB153 and 10 micromol/L PBDE-47 + 5 micromol/L PCB153 groups compared to the corresponding doses of PBDE-47 groups or PCB153 group (P < 0.05). The percentage of DNA in the tail and olive tail moment of cells treated by the groups added NAC were obviously lower than that of their corresponding groups not added it (P < 0.05). The interactive action was observed between PBDE-47 and PCB153 at concentrations of 10 micromol/L PBDE-47 (F = 23.74, P < 0.01). Significant decreased XRCC1 mRNA expression were observed at 10 micromol/L PBDE-47, 5 micromol/L PBDE-47 + 5 micromol/L PCB153, and 10 micromol/L PBDE-47 + 5 micromol/L PCB153 groups while significant increased XRCC3 mRNA expression were observed at 10 micromol/L PBDE-47 and 10 micromol/L PBDE-47 + 5 micromol/L PCB153 compared to the control group (P < 0.05). XRCC1 mRNA expression in cells treated by 100 micromol/L NAC + 10 micromol/L PBDE-47 + 5 micromol/L PCB153 group was significantly higher than that in 10 micromol/L PBDE-47 + 5 micromol/L PCB153 group (P < 0.05). XRCC3 mRNA expression in cells treated by PBDE-47 antioxidant groups were significantly lower than that in their corresponding non-antioxidant groups (P < 0.05). Correlation analysis showed there was a negative relationship between DNA damage and XRCC1 mRNA expression while a positive relationship between DNA damage and XRCC3 mRNA expression (r1 = 0.74, r2 = 0.76, P < 0.05).
PBDE-47 can induce DNA damage, PBDE-47 combined with PCB153 may increase the effects on DNA damage in SH-SY5Y cells in vitro, oxidative stress may play a important role in DNA damage induced by PBDE-47.
探讨多氯联苯153（PCB153）对2,2',4,4'-四溴联苯醚（PBDE-47）诱导的人神经母细胞瘤SH-SY5Y细胞DNA损伤及DNA修复相关基因表达的影响。
将SH-SY5Y细胞分别用不同浓度（1、5和10 μmol/L）的PBDE-47或/和5 μmol/L的PCB153以及抗氧化剂N-乙酰半胱氨酸（NAC，100 μmol/L）体外孵育24小时，分别检测DNA拖尾率、橄榄尾矩、X线修复交叉互补蛋白1（XRCC1）和X线修复交叉互补蛋白3（XRCC3）的mRNA表达水平。
与对照组相比，5 μmol/L及以上剂量的PBDE-47能显著增加DNA拖尾率和橄榄尾矩，且呈浓度依赖性（P < 0.05）。5 μmol/L PBDE-47 + 5 μmol/L PCB153组和10 μmol/L PBDE-47 + 5 μmol/L PCB153组细胞的DNA拖尾率和橄榄尾矩显著高于相应剂量的PBDE-47组或PCB153组（P < 0.05）。添加NAC组细胞的DNA拖尾率和橄榄尾矩明显低于未添加NAC的相应组（P < 0.05）。在10 μmol/L PBDE-47浓度下观察到PBDE-47与PCB153之间存在交互作用（F = 23.74，P < 0.01）。10 μmol/L PBDE-47组、5 μmol/L PBDE-47 + 5 μmol/L PCB153组和10 μmol/L PBDE-47 + 5 μmol/L PCB153组的XRCC1 mRNA表达显著降低，而10 μmol/L PBDE-47组和10 μmol/L PBDE-47 + 5 μmol/L PCB153组的XRCC3 mRNA表达显著高于对照组（P < 0.05）。100 μmol/L NAC + 10 μmol/L PBDE-47 + 5 μmol/L PCB153组细胞的XRCC1 mRNA表达显著高于10 μmol/L PBDE-47 + 5 μmol/L PCB153组（P < 0.05）。PBDE-47抗氧化剂组细胞的XRCC3 mRNA表达显著低于相应的非抗氧化剂组（P < 0.05）。相关性分析表明，DNA损伤与XRCC1 mRNA表达呈负相关，与XRCC3 mRNA表达呈正相关（r1 = 0.74，r2 = 0.76，P < 0.05）。
PBDE-47可诱导DNA损伤，PBDE-47与PCB153联合可能增强对体外SH-SY5Y细胞DNA损伤的作用，氧化应激可能在PBDE-47诱导的DNA损伤中起重要作用。
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