燃汽油机动车尾气致核酸分子氧化损伤效应研究

目的：通过研究燃汽油机动车尾气成分，及其对DNA分子的氧化损伤，在分子生物学水平上探讨燃汽油机动车尾气污染物的遗传毒性效应与机制。方法：以DNA加合物8-羟基脱氧鸟苷(8-OHdG)作为DNA氧化损伤的生物学标志物，用高压液相色谱-电化学检测(HPLC-EC)法对污染物染毒后的DNA中8-OHdG进行定量检测，通过气质联用法(GC-MS)进行有机成分分析和原子吸收法(AAS)对其进行无机元素分析，并从化学组成成分的角度探讨DNA氧化损伤的分子机理。结果：在燃汽油机动车尾气的颗粒物和挥发性有机物中分别检出有机污染物85种和46种，无机元素7种和5种。燃汽油机动车尾气颗粒物和挥发性有机物均可在体外直接诱导DNA氧化损伤，尾气颗粒物还可诱导大鼠肺组织DNA氧化损伤，并呈现一定的剂量—反应关系。结论：污染物直接以及间接的氧化作用，源于含有醌类、多酚等具有自氧化作用的化合物，不需要任何生物活化系统，在体外就可产生大量的活性氧自由基，并在金属离子的催化作用下进攻DNA的碱基形成8-OHdG，产生遗传毒性效应，而8-OHdG是DNA氧化损伤的较好的效应标志物。

A Study on the Oxidative DNA Damage Induced by Gasoline Vehicle Exhaust

Objective:The genotoxicity and its molecular mechanism of gasoline vehicle exhaust were studied through examining exhaust components and the oxidative DNA damage induced by them. Methods: DNA adduct,8-hydroxy deoxyguanosine (8-OHdG),was used as a biomarker of oxidative DNA damage. The level of 8-OHdG in DNA exposed to gasoline vehicle exhaust was measured by high performance liquid chromatography-electrochemical detection method(HPLC-EC) in vitro and in vivo. Organic and inorganic components in gasoline vehicle exhaust were analyzed by gas chromatography-mass spectrometry (GC-MS) and atomic absorption spectrometry(AAS)respectively. Results:There were 85 and 46 kinds of organic compounds, 7 and 5 kinds of inorganic compounds respectively in the particles and volatile organic compounds (VOCs) of gasoline vehicle exhaust. In addition,the particles and VOCs of gasoline vehicle exhaust could directly induce oxidative DNA damage.The particles could also induce oxidative DNA damage of rat lung tissues to form 8-OHdG with dose-response relationship. Conclusion: The main reason of the oxidative DNA damage is that gasoline vehicle exhaust contains a lot of polyphenol and quinone compounds which may further produce large amounts of active oxygen free radicals in vitro, without any biological activating system, to attack DNA and to form 8-OHdG and genotoxicity by the catalysis of metal ions. 8-OHdG is a better effect biomarker of oxidative DNA damage.