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目的研究2,2’,4,4’-四溴联苯醚(2,2’,4,4’-tetrabromodiphenyl ether,BDE47)的两种代谢物6-羟基-四溴联苯醚(6-OH-BDE47)和6-甲氧基-四溴联苯醚(6-OMe-BDE47)对人肝癌细胞HepG2的细胞毒性。方法 6-OH-BDE47和6-OMe-BDE47两个化合物均分别设1个溶剂对照(0.1%的DMSO)组和0.1、0.5和2.0μmol/L3个浓度染毒组。采用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法检测6-OH-BDE47和6-OMe-BDE47染毒6、24、48和72h后HepG2细胞的生长抑制效应,并检测24h急性染毒后细胞内活性氧(reactive oxygen,ROS)含量、超氧化物歧化酶(SOD)活力和谷胱甘肽(GSH)含量。结果 2.0、0.5、0.1μmol/L的6-OH-BDE47染毒组分别于染毒24、48和72h时出现HepG2细胞生长抑制效应(P<0.05或P<0.01),有剂量-效应关系;而2.0μmol/L的6-OMe-BDE47染毒组在染毒48h后才产生细胞生长抑制效应(P<0.05或P<0.01),0.5、0.1μmol/L的6-OMe-BDE47染毒组没有明显的细胞抑制效应(P>0.05)。24h急性染毒实验结果表明,各浓度6-OH-BDE47均能诱导HepG2细胞内ROS含量升高(P<0.01),2.0μmol/L的6-OH-BDE47染毒组能诱导SOD活力升高(P<0.01)、GSH含量下降(P<0.05);仅2.0μmol/L的6-OMe-BDE47染毒组可诱导ROS含量升高(P<0.01),未观察到6-OMe-BDE47对细胞SOD活力和GSH含量的影响(P>0.05)。结论 6-OH-BDE47和6-OMe-BDE47对HepG2的细胞有不同程度的生长抑制作用和氧化应激效应,前者作用较后者强。
Aim To investigate the effect of 6-hydroxy-tetrabromodiphenyl ether (6- (4,4’-tetrabromodiphenyl ether)), a metabolite of 2,2 ’, 4,4’-tetrabromodiphenyl ether (BDE47) OH-BDE47) and 6-methoxy-tetrabromodiphenyl ether (6-OMe-BDE47) on human hepatoma HepG2 cells. Methods Two compounds of 6-OH-BDE47 and 6-OMe-BDE47 were set up as 1 solvent control (0.1% DMSO) and 0.1, 0.5 and 2.0 μmol / L3 concentration groups respectively. The inhibitory effect of 6-OH-BDE47 and 6-OMe-BDE47 on the growth of HepG2 cells was detected by methyl thiazolyl tetrazolium (MTT) assay at 6, 24, 48 and 72 hours, and the intracellular activity Reactive oxygen species (ROS) content, superoxide dismutase (SOD) activity and glutathione (GSH) content. Results The growth inhibitory effect of HepG2 cells (P <0.05 or P <0.01) was observed in dose-dependent manner in 2.0, 0.5 and 0.1 μmol / L 6-OH- However, the effect of 6-OMe-BDE47 at 2.0 μmol / L was not inhibited by 6-OMe-BDE47 (P <0.05 or P <0.01) No obvious cytostatic effect (P> 0.05). The results of 24 h acute exposure showed that 6-OH-BDE47 could induce the increase of ROS in HepG2 cells (P <0.01), and the increase of SOD activity was induced by 2.0 μmol / L 6-OH-BDE47 (P <0.01), while the content of GSH decreased (P <0.05). Only 2.0 μmol / L 6-OMe-BDE47 could induce the increase of ROS content Cell SOD activity and GSH content (P> 0.05). Conclusions 6-OH-BDE47 and 6-OMe-BDE47 have different growth inhibition and oxidative stress effects on HepG2 cells, the former is stronger than the latter.