Oxy radicals, lipid peroxidation and DNA damage
Oxy radicals, lipid peroxidation and DNA damage
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DOI：
10.1016/s0300-483x(02)00448-1
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发表时间：
2002-12-27
期刊：
影响因子：
4.5
通讯作者：
Marnett, LJ
中科院分区：
文献类型：
--
作者：
Marnett, LJ
氧自由基与磷脂中的多不饱和脂肪酸残基反应，产生过多的产物，其中许多与蛋白质和DNA反应。丙二醛(MDA)是脂质过氧化作用中含量最丰富的羰基产物之一，也是前列腺素生物合成的副产物。它与DNA反应形成脱氧鸟苷、脱氧腺苷和脱氧胞苷的加合物。已在健康人的肝脏、白细胞、结肠、胰腺和乳房中检测到脱氧鸟苷加合物(M(I)G)，水平从每10(8)个核苷酸1到120个不等。随机和定点突变实验表明，丙二醛-DNA加合物在细菌和哺乳动物细胞中具有致突变性。当MiG被整合到病毒基因组中，然后在大肠杆菌中复制时，具有高度的突变性。它由核苷酸切除修复途径修复。脂质过氧化似乎是人类内源性DNA损伤的主要来源，可能会导致癌症和其他与生活方式和饮食因素有关的遗传性疾病。(C)2002年，爱思唯尔科学爱尔兰有限公司出版。
Oxygen radicals react with polyunsaturated fatty acid residues in phospholipids resulting in the production of a plethora of products, many of them reactive toward protein and DNA. One of the most abundant carbonyl products of lipid peroxidation is malondialdehyde (MDA), which also is generated as a side-product of prostaglandin biosynthesis. It reacts with DNA to form adducts to deoxyguanosine, deoxyadenosine, and deoxycytidine. The deoxyguanosine adduct (M(I)G) has been detected in liver, white blood cells, colon, pancreas, and breast from healthy human beings at levels ranging from 1 to 120 per 10(8) nucleotides. Random and site-specific mutagenesis experiments indicate that MDA-DNA adducts are mutagenic in bacteria and in mammalian cells. MIG is highly mutagenic when incorporated into viral genomes then replicated in E. coli. It is repaired by the nucleotide excision repair pathway. Lipid peroxidation appears to be a major source of endogenous DNA damage in humans that may contribute significantly to cancer and other genetic diseases linked to lifestyle and dietary factors. (C) 2002 Published by Elsevier Science Ireland Ltd.