OXIDATION OF DNA BASES, DEOXYRIBONUCLEOSIDES AND HOMOPOLYMERS BY PEROXYL RADICALS

DNA base oxidation is considered to be a key event associated with dis ease initiation and progression in humans. Peroxyl radicals (ROO.) are important oxidants found in cells whose ability to react with the DNA bases has not been characterized extensively. In this paper, the prod ucts resulting from ROO. oxidation of the DNA bases are determined by gas chromatography/MS in comparison with authentic standards. ROO. rad icals oxidize adenine and guanine to their 8-hydroxy derivatives, whic h are considered biomarkers of hydroxyl radical (HO.) oxidations in ce lls. ROO. radicals also oxidize adenine to its hydroxylamine, a previo usly unidentified product. ROO. radicals oxidize cytosine and thymine to the monohydroxy and dihydroxy derivatives that are formed by oxidat ive damage in cells. Identical ROO. oxidation profiles are observed fo r each base when exposed as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These results have significance for the d evelopment, utilization and interpretation of DNA base-derived biomark ers of oxidative damage associated with disease initiation and propaga tion, and support the idea that the mutagenic potential of N-oxidized bases, when generated in cellular DNA, will require careful evaluation Adenine hydroxylamine is proposed as a specific molecular probe for t he activity of ROO. in cellular systems.