Chapter 4. Oxidatively Induced DNA Damage: Mechanisms and Measurement

Oxidatively-induced damage to DNA occurs in living organisms by endogenously or exogenously generated reactive species, including free radicals. Mounting evidence suggests that this type of DNA damage plays an important role in the etiology of numerous disease processes, including carcinogenesis. Free radicals react with DNA bases and 2′-deoxyribose through a variety of mechanisms to generate a plethora of mutagenic and/or cytotoxic products. DNA repair pathways exist in living cells to restore DNA structure. Accurate measurement of DNA products is essential for understanding of mechanisms, cellular repair and biological consequences of oxidatively-induced DNA damage. Various analytical techniques with their own advantages and drawbacks are used for this purpose. Mass spectrometric techniques with isotope-dilution provide structural elucidation and accurate quantification of DNA products in vitro and in vivo such as DNA base and 2′-deoxyribose products, 8,5′-cyclopurine-2′-deoxynucleosides, base–base tandem lesions, and DNA–protein cross-links. This chapter reviews the mechanisms of product formation and the measurement of DNA products using mass spectrometric techniques. Repair and biological consequences of oxidatively induced DNA damage are also briefly discussed.