Lipid peroxidation - DNA damage by malondialdehyde

Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts wi th DNA to form adducts to deoxyguanosine and deoxyadenosine. The major addu ct to DNA is a pyrimidopurinone called M(1)G. Site-specific mutagenesis exp eriments indicate that M(1)G is mutagenic in bacteria and is repaired by th e nucleotide excision repair pathway. M(1)G has been detected in liver, whi te blood cells, pancreas, and breast from healthy human beings at levels ra nging from 1-120 per 10(8) nucleotides. Several different assays for M(1)G have been described that are based on mass spectrometry, P-32-postlabeling, or immunochemical techniques. Each technique offers advantages and disadva ntages based on a combination of sensitivity and specificity. Application o f each of these techniques to the analysis of M(1)G is reviewed and future needs for improvements are identified. M(1)G appears to be a major endogeno us DNA adduct in human beings that may contribute significantly to cancer l inked to lifestyle and dietary factors. High throughput methods for its det ection and quantitation will be extremely useful for screening large popula tions. (C) 1999 Elsevier Science B.V. All rights reserved.