汽车尾气提取物对hOGG1低表达细胞的氧化损伤作用  

Oxidative DNA Damage Induced by Automobile Emissions Extracts in Down-regulated Cells Expressed hOGG1 Genes

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作  者:吴媚[1] 张遵真[1] 车望军[1] 刘芳[1] 舒亚[1] 

机构地区:[1]四川大学华西公共卫生学院环境卫生教研室,成都610041

出  处:《环境与职业医学》2007年第2期153-156,共4页Journal of Environmental and Occupational Medicine

基  金:国家自然科学基金资助项目(编号:30571535)

摘  要:[目的]研究汽车尾气提取物对DNA碱基切除修复基因hOGG1低表达细胞的氧化损伤作用,为揭示汽车尾气提取物通过氧化损伤导致肺癌的发病机制提供更有力的证据。[方法]以肺腺癌A549细胞和通过稳定转染hOGG1核酶而使hOGG1低表达的A549-R细胞为研究对象,用MTT试验铡定汽车尾气提取物处理后两种细胞的生存能力;彗星试验检测两种细胞DNA损伤与修复的差异;并通过测定细胞内超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性,比较两种细胞抗氧化水平。[结果]A549-R细胞的IC50显著低于A549细胞(P<0.05);汽车尾气提取物作用下两种细胞均有不同程度DNA损伤,A549-R细胞的拖尾率和DNA迁移长度显著大于A549细胞(P<0.05);损伤后A549细胞修复发生较A549-R快,与A549细胞相比A549-R细胞更不易修复;汽车尾气提取物作用下两种细胞内SOD及GSH-Px活性均下降,A549-R细胞的抗氧化水平较A549细胞更低。[结论]hOGG1低表达使肺腺癌细胞:DNA修复能力降低,从而使其对汽车尾气提取物的敏感性增强,汽车尾气提取物可能通过氧化损伤途径导致肺癌的发生。[ Objective ] To investigate the oxidative damage induced by automobile emissions extracts in down-regulated cells expressed hOGG1 genes which targets to oxidative DNA damage and repair, and provide more evidence to the viewpoint that automobile emissions extracts induces lung cancer by oxidative damage. [ Methods ] Take human lung adenocarcinoma A549 cells as the target of our study, as well as the A549-R cells into which ribozyme genes were transfected for inhibiting the hOGG1 mRNA expression. The cell viability after treatment of automobile emissions extracts was detected by MTr test. DNA damage and repair were detected by comet assay. The antioxidative ability was evaluated by detecting activity of SOD and GSH-Px in cells. [ Results ] The cell viability after treatment was decreased as denoted by that ICs0 of automobile emissions extracts was significantly lower in A549-R ceils than in A549 ceils( P〈0.05 ). Automobile emissions extracts can induce DNA damage to the two kinds of cells, and the damage in A549-R cells was more serious than in A549 cells as both denoted in comet cell rate and DNA migration length. The DNA repair after treatment of automobile emissions extracts happened earlier in A549 cells than in A549-R cells. It showed the repair capability in the latter was significantly lower than that in the former. [ Conclusion ] Down-regulating of the expression of hOGG1 can decrease the DNA repair capability of A549 cells, and increase their sensitivity to automobile emissions extracts. The viewpoint that automobile emissions extracts induce lung cancer by oxidative damage is credible.

关 键 词:汽车尾气提取物 HOGG1 氧化损伤 肺癌 

分 类 号:X51[环境科学与工程—环境工程]

 

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