外源性还原型谷胱甘肽对亚砷酸钠诱导遗传毒性及氧化应激的保护作用  

Protective effects of exogenous reduced glutathione on sodium arsenite-induced genotoxicity and oxidative stress

作　　者：陈承志[1] 蒋学君[1] 张遵真[1] 

机构地区：[1]四川大学华西公共卫生学院环境卫生学教研室,成都610041

出　　处：《卫生研究》2013年第6期937-942,949,共7页Journal of Hygiene Research

基　　金：国家自然科学基金(No.81172632)

摘　　要：目的探讨外源性还原型谷胱甘肽（GSH）能否拮抗亚砷酸钠（NaAsO2）诱导的遗传毒性及氧化损伤。方法以人肺腺癌A549细胞为研究对象，按处理方式分为对照组、单独NaAsO2或GSH处理组及不同浓度GSH和NaAsO2联合组，观察GSH处理对细胞存活、氧化应激水平、DNA单链断裂及染色体损伤的影响。结果NaAsO2单独染毒处理可导致细胞存活率、集落形成率、SOD酶活性和GSH含量低于对照组，而ROS水平、彗星率、Oliver尾距和微核细胞率较对照组增加（P〈0．05）。GsH浓度为0．5—5mmol／L时，联合处理组与单独NaAsO2处理组比较上述各项检测指标差异无显著性；而当GSH剂量为10和20mmol／L时，NaAsO2处理产生的毒性作用虽有所改善，却仍显著低于对照组（P〈0．05）；随着GSH剂量水平的增加，在GSH为40或50mmol／L时，细胞存活、集落形成、氧化应激水平及DNA和染色体损伤情况与对照组比较差异已无显著性。结论外源性添加高浓度的GSH能够显著减弱NaAsO2的细胞毒性，减轻DNA、染色体损伤及氧化应激水平。Objective To explore the protective effects of exogenous reduced glutathione （GSH） on the genotoxieity and oxidative stress induced by sodium arsenite （NaAsO2 ）. Methods Human lung adenoearcinoma A549 cells were divided into several groups according to the treatments as follow： untreated group, single NaAsO2 or GSH treated group and the groups co-treated with NaAsO2and different concentrations of GSH. Then the differences of cell viability, level of oxidative stress, DNA and chromosomal damage were compared after single or combined treatments. Results The rate of cell survival and colony formation, the contents of GSH and the activity of SOD in NaAsO2 treated group were significantly lower than the non-treated group, whereas, the level of ROS, comet rate, OTM and the frequency of micronucleus in NaAsO2 treated group were significantly higher than that of control group （P 〈 0.05）. At the 0.5 - 5mmol/L concentrations of GSH, these indicators of the co-treatment groups did not show any significant difference when compared with single NaAsOz-treated group. However, at the 10 mmol/L and 20 mmol/L concentrations of GSH, the NaAsO2-induced toxic effects were found to be weakened by GSH, but it was still significantly lower than that in the control group （P 〈 0.05）. Moreover, there was no significant difference among co-treated groups and control group on the cell viability, colony formation, level of oxidative stress and DNA and chromosomal damage at the 40 or 50 mmol/L of GSH. Conclusion High concentrations of exogenous GSH can significantly decrease the cytotoxicity of NaAsO2, and alleviate DNA and chromosomal damage and the level of oxidative stress.

关 键 词：亚砷酸钠 谷胱甘肽 DNA损伤 染色体断裂 氧化应激 

分 类 号：R994.6[医药卫生—毒理学] R734.2[医药卫生—药学]