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(1)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. M(1)G 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.