Affiliation:
1. Department of Pharmaceutical Sciences, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2303, U.S.A.
Abstract
DNA base oxidation is considered to be a key event associated with disease 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 products resulting from ROO• oxidation of the DNA bases are determined by gas chromatography/MS in comparison with authentic standards. ROO• radicals oxidize adenine and guanine to their 8-hydroxy derivatives, which are considered biomarkers of hydroxyl radical (HO•) oxidations in cells. ROO• radicals also oxidize adenine to its hydroxylamine, a previously unidentified product. ROO• radicals oxidize cytosine and thymine to the monohydroxy and dihydroxy derivatives that are formed by oxidative damage in cells. Identical ROO• oxidation profiles are observed for each base when exposed as deoxyribonucleosides, monohomopolymers and base-paired dihomopolymers. These results have significance for the development, utilization and interpretation of DNA base-derived biomarkers of oxidative damage associated with disease initiation and propagation, 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 the activity of ROO• in cellular systems.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
66 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Theoretical Study of 5,5,6-Trihydroxy-6-methyldihydropyrimidine-2,4-dione Enantiomers;Russian Journal of Physical Chemistry A;2023-10
2. Теоретическое исследование энантиомеров 5,5,6-тригидрокси-6-метилдигидропиримидин-2,4-диона;Журнал физической химии;2023-10-01
3. MoaE Is Involved in Response to Oxidative Stress in Deinococcus radiodurans;International Journal of Molecular Sciences;2023-01-26
4. An NMR Spectral Study of the Structure of 5,5,6-trihydroxy-6-methyldihydropyrimidine-2,4-(1H,3H)-dione in DMSO-d6;Journal of Applied Spectroscopy;2022-05
5. STRUCTURE INVESTIGATION OF 5,5,6-TRIHYDROXY-6-METHYLDIHYDROPYRIMIDINE-2,4(1H,3H)-DIONE IN DMSO-d6 SOLUTION BY NMR-SPECTROSCOPY;Journal of Applied Spectroscopy;2022-03-18