Marnett L J
A.B. Hancock Jr. Memorial Laboratory for Cancer Research Center in Molecular Toxicology, Vanderbilt Cancer Center, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville TN 37232, USA.
Mutat Res. 1999 Mar 8;424(1-2):83-95. doi: 10.1016/s0027-5107(99)00010-x.
Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is a pyrimidopurinone called M1G. Site-specific mutagenesis experiments indicate that M1G is mutagenic in bacteria and is repaired by the nucleotide excision repair pathway. M1G has been detected in liver, white blood cells, pancreas, and breast from healthy human beings at levels ranging from 1-120 per 108 nucleotides. Several different assays for M1G have been described that are based on mass spectrometry, 32P-postlabeling, or immunochemical techniques. Each technique offers advantages and disadvantages based on a combination of sensitivity and specificity. Application of each of these techniques to the analysis of M1G is reviewed and future needs for improvements are identified. M1G appears to be a major endogenous DNA adduct in human beings that may contribute significantly to cancer linked to lifestyle and dietary factors. High throughput methods for its detection and quantitation will be extremely useful for screening large populations.
丙二醛是脂质过氧化和前列腺素生物合成的天然产物，具有致突变性和致癌性。它与DNA反应形成与脱氧鸟苷和脱氧腺苷的加合物。DNA的主要加合物是一种称为M1G的嘧啶嘌呤酮。位点特异性诱变实验表明，M1G在细菌中具有致突变性，并通过核苷酸切除修复途径进行修复。在健康人的肝脏、白细胞、胰腺和乳腺中已检测到M1G，其水平为每108个核苷酸1 - 120个。已经描述了几种基于质谱、32P后标记或免疫化学技术的M1G不同检测方法。每种技术基于灵敏度和特异性的组合都有其优缺点。综述了这些技术在M1G分析中的应用，并确定了未来改进的需求。M1G似乎是人类主要的内源性DNA加合物，可能对与生活方式和饮食因素相关的癌症有重大贡献。其检测和定量的高通量方法对于筛查大量人群将极为有用。
