Combination of Nitrogen Dioxide Radicals with 8-Oxo-7,8-dihydroguanine and Guanine Radicals in DNA: Oxidation and Nitration End-Products

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• 作者：Richard Misiaszek ; Conor Crean ; Nicholas E. Geacintov ; and Vladimir Shafirovich
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：February 23, 2005
• 年：2005
• 卷：127
• 期：7
• 页码：2191 - 2200
• 全文大小：183K
• 年卷期：v.127,no.7(February 23, 2005)
• ISSN：1520-5126

文摘

The oxidation and nitration reactions in DNA associated with the combination of nitrogen dioxideradicals with 8-oxo-7,8-dihydroguanine (8-oxoGua) and guanine radicals were explored by kinetic laserspectroscopy and mass spectrometry methods. The oxidation/nitration processes were triggered byphotoexcitation of 2-aminopurine (2AP) residues site-specifically positioned in the 2'-deoxyribooligonucleotide5'-d(CC[2AP]TC[X]CTACC) sequences (X = 8-oxoGua or G), by intense 308 nm excimer laser pulses.The photoionization products, 2AP radicals, rapidly oxidize either 8-oxoGua or G residues positioned withinthe same oligonucleotide but separated by a TC dinucleotide step on the 3'-side of 2AP. The two-photonionization of the 2AP residue also generates hydrated electrons that are trapped by nitrate anions thusforming nitrogen dioxide radicals. The combination of nitrogen dioxide radicals with the 8-oxoGua and Gradicals occurs with similar rate constants (~4.3 × 10⁸ M^-1 s^-1) in both single- and double-stranded DNA.In the case of 8-oxoGua, the major end-products of this bimolecular radical-radical addition arespiroiminodihydantoin lesions, the products of 8-oxoGua oxidation. Oxygen-18 isotope labeling experimentsreveal that the O-atom in the spiroiminodihydantoin lesion originates from water molecules, not from nitrogendioxide radicals. In contrast, combination of nitrogen dioxide and guanine neutral radicals generated underthe same conditions results in the formation of the nitro products, 5-guanidino-4-nitroimidazole and8-nitroguanine adducts. The mechanistic aspects of the oxidation/nitration processes and their biologicalimplications are discussed.