Keynote address: exocyclic adducts as new risk markers for DNA damage in man.

Background levels of exocyclic DNA adducts detected by ultrasensitive methods in tissues from unexposed humans and rodents arise from endogenous lipid peroxidation products such as trans-4-hydroxy-2-nonenal, crotonaldehyde and malondialdehyde. The levels of DNA adducts in rodent and human tissues and leukocytes were found to be highly variable and to be affected by lifestyle, the dietary intake of antioxidants and the type and amount of fatty acids and persistent chronic infections or inflammations, in which nitric oxide is often over-produced. Limited evidence suggests that etheno-DNA adducts play a role not only in vinyl chloride- and urethane-induced tumorigenesis but, together with other exocyclic lesions, also in several human cancers in which persistent oxidative stress leads to malignancy by increasing mutation rates and genomic instability. Therefore, promutagenic exocyclic adducts appear to be promising markers in molecular epidemiological studies for identifying endogenous sources of DNA damage and resulting oxidative modifications in cancers with poorly defined etiology and mechanisms and in intervention studies to assess the protective effects of antioxidants against cancer and, possibly, neurodegenerative diseases.