Exocyclic DNA adducts as secondary markers for oxidative stress: applications in human cancer etiology and risk assessment.

Abstract

DNA-bound carcinogen adducts reflect the amount of an exogenous chemical or its metabolite that covalently interacted with nucleic acid bases at the target site (biologically effective dose) or in surrogate tissues. DNA adducts are mechanistically more relevant to carcinogenesis than internal doses of genotoxins, since they take into account interindividual differences in metabolism and of DNA repair capacity. The rationale for measuring DNA adducts as relevant dosimeters of biological effects and predictor of cancer risk is derived from extensive experimental and human data, supporting their role in the initiation and probably the progression of cancer. Several hundreds of DNA adducts, many with miscoding properties, are known to be produced by some 20 classes of carcinogens and through endogenous processes including oxidized DNA bases (Hemminki et al., 1994). These lesions provide powerful tools for studying disease pathogenesis, etiology and for verifying preventive measures in human cancer or other chronic degenerative diseases.