ETHENO-DNA BASE ADDUCTS AS TOOLS IN HUMAN CANCER ETIOLOGY AND CHEMOPREVENTION

Etheno adducts in DNA are formed from the carcinogens vinyl chloride a nd urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method , the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that d evelop hepatitis and hepatocellular carcinoma. Wilson's disease and pr imary haemochromatosis are human genetic disorders that cause copper o r iron accumulation resulting in a high risk for primary liver cancers . Levels of etheno adducts were also significantly elevated in the liv er of these patients. In a group of male and female volunteers kept on a controlled diet, the effect of dietary fatty acid composition on th e endogenous formation of lipid peroxidation-derived DNA adducts was d etermined in DNA from white blood cells. Dietary omega-6-polyunsaturat ed fatty acids greatly increased LPO-derived etheno-DNA adducts in viv o, in females. Thus, exocyclic DNA adducts are promising biomarkers fo r elucidating the effect of dietary fat intake, oxidative stress and p rotective dietary antioxidants on endogenous DNA damage and thus may p rovide a possible mechanistic link with elevated risk for diet-related cancers.