Łuczaj Wojciech, Skrzydlewska Elzbieta
Department of Analytical Chemistry, Medical Academy of Białystok, Mickiewicza 2A, P.O. Box 14, 15-230 Białystok 8, Poland.
Cell Mol Biol Lett. 2003;8(2):391-413.
Lipid peroxidation is a process involving the oxidation of polyunsaturated fatty acids (PUFAs), which are basic components of biological membranes. Reactive electrophilic compounds are formed during lipid peroxidation, mainly alpha, beta-unsaturated aldehydes. These compounds yield a number of adducts with DNA. Among them, propeno and substituted propano adducts of deoxyguanosine with malondialdehyde (MDA), acrolein, crotonaldehyde and etheno adducts, resulting from the reactions of DNA bases with epoxy aldehydes, are a very important group of adducts. The epoxy aldehydes are more reactive towards DNA than the parent unsaturated aldehydes. The compounds resulting from lipid peroxidation mostly react with DNA showing both genotoxic and mutagenic action; among them, 4-hydroxynonenal is the most genotoxic, while MDA is the most mutagenic. DNA damage caused by the adducts of lipid peroxidation products with DNA can be removed by the repairing action of glycosylases. The formed adducts have been hitherto analyzed using the IPPA (Imunopurification-(32)P-postlabelling assay) method and via gas chromatography/electron capture negtive chemical ionization/mass spectrometry (GC/EC NCI/MS). A combination of liquid chromatography with electrospray tandem mass spectrometry (LC/ES-MSMS) with labelled inner standard has mainly been used in recent years.
脂质过氧化是一个涉及多不饱和脂肪酸（PUFAs）氧化的过程，多不饱和脂肪酸是生物膜的基本组成成分。在脂质过氧化过程中会形成反应性亲电化合物，主要是α,β-不饱和醛。这些化合物会与DNA产生多种加合物。其中，脱氧鸟苷与丙二醛（MDA）、丙烯醛、巴豆醛形成的丙烯醛和取代丙烷加合物，以及DNA碱基与环氧醛反应生成的乙烯基加合物，是非常重要的一类加合物。环氧醛对DNA的反应性比母体不饱和醛更强。脂质过氧化产生的化合物大多与DNA发生反应，表现出基因毒性和致突变作用；其中，4-羟基壬烯醛的基因毒性最强，而丙二醛的致突变性最强。脂质过氧化产物与DNA形成的加合物所导致的DNA损伤可通过糖基化酶的修复作用去除。迄今为止，已使用免疫纯化 -（32）P后标记分析法（IPPA）以及气相色谱/电子捕获负离子化学电离/质谱法（GC/EC NCI/MS）对所形成的加合物进行分析。近年来主要使用的是液相色谱与电喷雾串联质谱法（LC/ES-MSMS）结合标记内标物的方法。
