Prof. Dr. Mustafa Birincioğlu
Measurement of oxidative DNA damage by liquid chromatography/mass spectrometry.
11th Biennial Meeting of the Society for Free Radical Research International. Paris, France, 2002
Publication year: 2002
Oxidative DNA damage results from reactions of oxygen-derived species including free radicals, most notably hydroxyl radical, with the four heterocyclic bases
and sugar moiety in DNA (reviewed in [1,2]). Reactions of free radicals result in a plethora of DNA products that comprise modified bases and sugars, DNA–protein
crosslinks, strand breaks, clustered lesions and tandem lesions such as 8,5-cyclopurine 2-deoxynucleosides. Many of these products are genotoxic, leading to cell death and
mutations (reviewed in [3]). Hydroxyl radicals can be generated in cells by ionizin gradiation from cellular water or by reactions of superoxide radical and H2O2with tran-
sition metal ions. Hydroxyl radicals react with DNA components at or near diffusion controlled reaction rates by addition to double bonds of heterocyclic DNA bases and
by abstraction of an H atom from the methyl group of thymine and from each of the CH bonds of 2-deoxyribose [4]. Subsequent reactions of thus-formed base and sugar
radicals result in numerous products. Figure 3.1 illustrates the structures of the major modified DNA bases and 8,5-cyclopurine 2-deoxynucleosides. Unless repaired by
complex DNA repair mechanisms in cells (reviewed in [5]), oxidative DNA damage can lead to a broad range of pathophysiological processes including carcinogenesis,
neurological disorders and aging (reviewed in [3,6,7]). Accurate measurements are essential for the understanding of mechanisms and cellular repair of oxidative DNA
damage, and its role in disease processes.