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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0.5~5 mmol/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20 mmol/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50 mmol/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 investigate whether exogenous reduced glutathione (GSH) can antagonize the genetic toxicity and oxidative damage induced by sodium arsenite (NaAsO2). Methods Human lung adenocarcinoma A549 cells were divided into control group, treatment group with NaAsO2 or GSH alone and combination of different concentrations of GSH and NaAsO2. The effects of GSH on cell survival, oxidative stress, DNA single strand Fracture and chromosome damage. Results Exposure of NaAsO2 alone resulted in lower cell viability, colony formation rate, SOD activity and GSH content than the control group, but ROS level, comet rate, Oliver tail and micronucleus rate increased compared with the control group (P <0.05 ). When the concentration of GSH was 0.5-5 mmol / L, there was no significant difference between the combination treatment group and the NaAsO2 alone treatment group. When the GSH concentration was 10 and 20 mmol / L, the toxic effect of NaAsO2 treatment (P <0.05). With the increase of GSH dose, the cell viability, colony formation, oxidative stress and DNA and chromosome were significantly increased at GSH of 40 or 50 mmol / L There was no significant difference between the injury and the control group. Conclusion Exogenously added high concentration of GSH can significantly reduce the cytotoxicity of NaAsO2 and reduce DNA, chromosome damage and oxidative stress.