Lipid peroxidation-induced etheno-DNA adducts in humans

Increased oxidative stress and lipid peroxidation are implicated at various stages of carcinogenic processes. Recent studies have shown that reactive hydroxyalkenals derived from lipid peroxidation form the promutagenic exocyclic etheno DNA adducts 1,N6-ethenodeoxyadenosine (epsilon dA) and 3,N4-ethenodeoxycytidine (epsilon dC). A highly selective and sensitive immunoaffinity 32P-postlabelling method has been developed to detect epsilon dA and epsilon dC, with a detection limit of about 5 adducts per 10(10) parent nucleotides, which permitted their measurement in small amounts of human DNA. Background levels of epsilon dA and epsilon dC were detected in normal human tissue DNA, apparently as a result of lipid peroxidation under normal physiological conditions. High levels of epsilon dA and epsilon dC were found in the liver DNA of cancer-prone patients with Wilson disease or primary haemochromatosis. High dietary intake of omega-6 polyunsaturated fatty acids, which are readily oxidized to form enals, increased the epsilon dA and epsilon dC levels in DNA from leukocytes of women. An immunoaffinity-high-performance liquid chromatography-fluorescence method has been developed to measure epsilon dA in human urine. Etheno DNA adducts can now be used as biomarkers to investigate the potential role of oxidative stress and lipid peroxidation in human cancers associated with certain lifestyles or chronic infections and to verify whether the levels of these adducts can be reduced by chemopreventive regimens.