6-羟基联合甲氧基-四溴联苯醚47对HepG2的细胞毒性研究  

Cytotoxicity of 6-hydroxylated/6-methoxylated-2,2’,4,4’-tetrabromodiphenyl Ether to HepG2 Cells

作　　者：钟玉芳[1] 尹灵灵[1] 赵晓华[2] 安静[1] 

机构地区：[1]上海大学环境与化学工程学院环境污染与健康研究所 [2]中国人民解放军93321部队

出　　处：《环境与健康杂志》2010年第6期477-479,共3页Journal of Environment and Health

基　　金：国家"973"计划项目(2008CB41820);上海市重点学科(第三期)项目(S30109)

摘　　要：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。Objective To study the cytoxicity of 6-hydroxylated/6-methoxylated-2,2＇,4,4＇-tetrabromodiphenyl ether （6-OH and 6-OMe-BDE47）to human liver cancer cell line - HepG2. Methods Seven groups （ 0.1% DMSO,0.1 μmol/L,0.5 μmol/L and 2.0 μmol/L 6-OH and 6-OMe-BDE47 ）were set in this study. HepG2 cells proliferation was detected after 6 h, 24 h, 48 h and 72 h of exposure with MTT test; intracellular reactive oxygen（ROS）, superoxide dismutase （SOD） and glutathione （GSH） were measured after cells were treated with 6-OH/6-OMe-BDE47 as above-mentioned doses for 24 h. Results 2.0 p, mol/L, 0.5 μmol/L and 0.1 p, mol/L 6-OH-BDE47 caused significant cell proliferation inhibition after exposure for 24 h,48 h and 72 h respectively, only 2.0 μmol/L 6-OMe-BDE47 showed cell proliferation inhibition after exposure for 48 h, there was no cell proliferation inhibition in 0.5, 0.1 μmol/L groups; after acute exposure for 24 h,6-OH-BDE47 induced elevation of intracellular ROS with a dose-dependent manner,and 6-OMe-BDE47 increased intracellular ROS at dose of 2.0 p, mol/L; The activity of SOD in HepG2 increased and glutathione decreased in 2.0 μmol/L 6-OH-BDE47 group,while no significant change of SOD activity and GSH content caused by 6-OMe-BDE47 were observed at the doses above-mentioned. Conclusions 6-OH-BDE47 and 6-OMe-BDE47 induced cell proliferation inhibition and oxidative stress effects to HepG2 cells in degrees,6-OH-BDE47 showed more stronger toxic effects than 6-OMe-BDE47.

关 键 词：多溴联苯醚 2 2’ 4 4’-四溴联苯醚 持久性有机污染物 氧化应激 

分 类 号：R994.6[医药卫生—毒理学]