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Emphasis was placed in this work on the measurement of purine oxidation products generated upon nano- and picosecond UV laser biphotonic photolysis of 2‘-deoxyadenosine, 2‘-deoxyguanosine, calf thymus DNA, and a synthetic duplex oligonucleotide (37-mer) in aerated aqueous solutions. The overall formation of 8-oxo-7,8-dihydro-2‘-deoxyguanosine and 8-oxo-7,8-dihydro-2‘-deoxyadenosine was determined using a HPLC-electrochemical detection assay. Denaturing gel electrophoresis analysis in association with a formamidopyrimidine−DNA glycosylase treatment was applied to reveal the sites recognized by this DNA repair enzyme. Both 8-oxo-7,8-dihydro-2‘-deoxyguanosine and 8-oxo-7,8-dihydro-2‘-deoxyadenosine were shown to be minor decomposition products of the related nucleoside purine radical cations in agreement with earlier observations. Interestingly, a dramatic increase in the yield of both photoproducts, this applying particularly to 8-oxo-7,8-dihydro-2‘-deoxyguanosine, was observed in DNA. It should be noted that the yield of 8-oxo-7,8-dihydro-2‘-deoxyguanosine was about 3-fold lower in heat-denatured DNA than in double-stranded DNA. These observations provide strong support to the significant involvement of base stacking and probably DNA solvatation in the chemical reactions of the purine radical cations. Other interesting information dealt with the similarity in the level of 8-oxo-7,8-dihydro-2‘-deoxyguanosine and the number of formamidopyrimidine−DNA glycosylase sensitive guanine lesions. This strongly suggests that the latter formamidopyrimidine−DNA glycosylase purine nucleoside is the major DNA photodamaged product recognized by the DNA repair glycosylase. Another striking feature is the almost 10-fold decrease in the saturation dose E s for the two-quantum ionization of the guanine base in double-stranded DNA as compared to that observed for free 2‘-deoxyguanosine. This can be explained by either an enhancement of the quantum yield of photoionization from the intermediate excited state in DNA (φ2) and/or hole migration with preferential trapping by guanine residues.

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This review discusses recent aspects of oxidation reactions of DNA and model compounds involving mostly OH radicals, one-electron transfer process and singlet oxygen (1O2). Emphasis is placed on the formation of double DNA lesions involving a purine base on one hand and either a pyrimidine base or a 2-deoxyribose moiety on the other hand. Structural and mechanistic information is also provided on secondary oxidation reactions of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a major DNA marker of oxidative stress. Another major topic which is addressed here deals with recent developments in the measurement of oxidative base damage to cellular DNA. This has been mostly achieved using the accurate and highly specific HPLC method coupled with the tandem mass spectrometry detection technique. Interestingly, optimized conditions of DNA extraction and subsequent work-up allow the accurate measurement of 11 modified nucleosides and bases within cellular DNA upon exposure to oxidizing agents, including UVA and ionizing radiations. In addition, the modified comet assay, which involves the use of bacterial DNA N-glycosylases to reveal two main classes of oxidative base damage, is applicable to isolated cells and is particularly suitable when only small amounts of biological material are available. Finally, recently available data on the substrate specificity of DNA repair enzymes belonging to the base excision pathways are briefly reviewed.

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The bulk of the radiation-induced degradation products of 2′-deoxyguanosine in oxygen-free aqueous solution have been separated by high performance liquid chromatography and charac­terized by various spectroscopic techniques including fast atom bombardment mass spectrometry, 1H NMR and circular dichroism. The two main decomposition products result from the opening of the imidazole ring and further rearrangement of the sugar moiety. In addition, the formation of six other nucleosides was shown to involve sugar radicals with subsequent epimerization, re­arrangement or cyclization reactions.