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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.

The reaction of Haat [Haat = (3-acetylamino-1,2,4-triazole)] with aquated Cu(CF3SO3)2, Cu(NO3)2, and Cu(ClO4)2, respectively, in water results in the trinuclear complexes [Cu3(OH)(aat)3(CF3SO3)(H2O)2](CF3SO3) (1), [Cu3(OH)(aat)3(NO3)(H2O)2](NO3).(H2O)2 (2), and [Cu3(OH)(aat)3(ClO4)(H2O)2](ClO4) (3). The synthesis, X-ray structure, and magnetic and spectroscopic properties of the three title complexes are described. The cation of the three complexes is trinuclear with a Cu3OH skeleton which has the N-N diazine grouping of a triazole ring as bridge between each pair of copper atoms. The Cu3OH units have an average Cu-O distance of 1.991(6) (1), 2.000(6) (2), and 2.007(6) (3) A, an average Cu-Cu' distance of 3.355(2) (1), 3.341(1) (2), and 3.371(3) (3) A, and an average Cu-O-Cu' angle of 114.6(3) degrees (1), 112.4(2) degrees (2), and 115.4(3) degrees (3). The existence of the Cu3OH fragment is confirmed by a pseudotetrahedral oxygen environment, by detection of the OH hydrogen atom, and by stoichiometry. In the trinuclear unit the metal ions show, in the first approximation, a pseudo-square-planar pyramidal environment forming a CuN2O3 chromophore; three of the basal positions are occupied by N,N,O aat ligand atoms, the fourth one is occupied by the oxygen of the central OH group, and the apical site is occupied by an oxygen atom from a water molecule in the case of two of the copper(II) atoms and by an oxygen atom from the coordinating anion in the case of the third metal ion. The three compounds exhibit strong antiferromagnetic interaction, with similar J constants [J = -197.7 (1), J = -190.9 (2), J = -198.2 (3) cm-1], reaching complete spin coupling at ca. 75 K (1)/55 K (2)/95 K (3). At very low temperature the magnetic moment (magnetic susceptibility) falls below that expected for one unpaired electron. Magnetic parameters are discussed on the basis of the structural results and compared with those reported in the literature for related trimeric Cu(II) compounds with N-O or N-N peripheral bridges. Solid state EPR spectra of the three complexes recorded at liquid N temperature show axial signals. Crystal data: C14H20Cu3F6N12O12S2 (1) (Mw = 917.16) crystallizes in the monoclinic space group, P2(1)/c, Z = 4, with cell dimensions a = 13.080(2) A, b = 17.202(2) A, c = 13.840(2) A, beta = 92.40(1) degrees, and V = 3111.3(7) A3, Dcalcd = 1.958 Mg m-3; the final agreement values were R1 = 0.0582 and wR2 = 0.1462 for 7107 unique reflections. C12H24Cu3N14O14 (2) (Mw = 779.07) crystallizes in the triclinic space group, P1, Z = 2, with cell dimensions a = 9.647(2) A, b = 9.985(2) A, c = 15.314(2) A, alpha = 84.080(10), beta = 87.694(10), gamma = 65.030(10) degrees, and V = 1330.1(4) A3, Dcalcd = 1.945 Mg m-3; the final agreement values were R1 = 0.0397 and wR2 = 0.0950 for 7728 unique reflections. C12H20Cl2Cu3N12O14 (3) (Mw = 817.92) crystallizes in the monoclinic space group, P2(1)/a, Z = 4, with cell dimensions a = 14.238(5) A, b = 16.387(6) A, c = 11.678(4) A, gamma = 90.45(2) degrees, and V = 2724.6(18) A3, Dcalcd = 1....

Most of the reactions induced by *OH radicals (indirect effects) and by one-electron oxidation (direct effects) as the result of exposure to ionizing radiation may be described for the four main DNA nucleobases. Relevant information is now available on the formation of single and tandem base lesions implicating guanine as the most susceptible DNA component to the deleterious effects of ionizing radiation. In contrast, there is still a paucity of information on the radiation-induced formation of base damage within cellular DNA. This is mostly a result of difficulties associated with the measurement of oxidized purine and pyrimidine bases that appear to be generated in very low yields. This is illustrated by the measurement of low amounts of E. coli formamidopyrimidine glycosylase- and endonuclease-III-sensitive sites in the DNA of neoplastic monocytes upon exposure to gamma rays (48 and 53 per 10(9) bases and per Gy, respectively) using a modified comet assay (the overall number of strand breaks and alkali-labile sites was estimated to be 130 per 10(9) bases and per Gy). More specifically, the level of several radiation-induced modified bases, including thymine glycols, 5-formyluracil, 5-(hydroxymethyl)uracil, 8-oxo-7,8-dihydroguanine, and 8-oxo-7,8-dihydroadenine, together with related formamidopyrimidine derivatives was assessed using the suitable HPLC-MS/MS method. Information is also provided on the substrate specificity of DNA repair enzymes and the mutagenic potential of base lesions using site-specific modified oligonucleotides as the probes.