Oxaluric Acid as the Major Product of Singlet Oxygen-Mediated Oxidation of 8-Oxo-7,8-dihydroguanine in DNA

Abstract

Oxidative reactions of DNA commonly result in base modifications. Among the four DNA bases, guanine is the most susceptible to oxidation, and one of its main oxidized compounds, namely 8-oxo-7,8-dihydroguanine (8-oxoGua), has been extensively studied in terms of formation, repair, and mutagenicity. However, the latter modified purine base is readily subjected to further oxidation reactions which have recently become a matter of interest. Emphasis was placed in this work on the identification of the final singlet oxygen oxidation products of 8-oxoGua in single-stranded DNA. Oxaluric acid was found to be the predominant product of the reaction. Insights in the mechanistic pattern of oxaluric acid formation were gained from isotopic labeling experiments in association with mass spectrometry measurements. It was found that oxaluric acid is formed via an oxidized guanidinohydantoin intermediate, arising from the likely degradation of a transient 5-hydroperoxide. Two subsequent hydrolytic steps that are accompanied by the release of guanidine are likely to be involved in the formation of oxaluric acid.

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

“…Another argument that supports this hypothesis is that laser excitation of the radicals results in the formation of dehydroguanidinohydantoin lesions as the major product. The latter lesions slowly transform to the oxaluric acid lesions as reported earlier (43,44).…”

Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanosine oxidation

“…Product 1 was therefore proposed to be oxidised Guanidinohydantoin, Gh ox , based on previous studies which indicated that this 290 compound, which has been shown to be unusually stable, was a main product of 8-oxoGua oxidation. 11 were about one third lower than for corresponding iron incubations.…”

“…Sp, Iz and Oz were detected on oxidation of 8-oxodGuo by chemically induced 1 O 2 , 12 with Oxa detected on oxidation of single stranded oligomers 60 containing 8-oxodGuo. 11 Hydroxyl radical (•OH) oxidation of dG was found to generate Oz under reducing conditions, 13 however, for •OH oxidation induced by iron (II) ions, further oxidation of 8-oxoGua was expected to be prevented. 14 Photoirradiation produced Iz as the major product of DNA 65 oxidation.…”

Changes in the Spin State and Reactivity of Cytochrome c Induced by Photochemically Generated Singlet Oxygen and Free Radicals

“…This excited species, which can be generated by an energy transfer mechanism (6,7), exhibits high reactivity and can be produced in biological systems (8,9). In mammalian cells, O 2 ( 1 ⌬ g ) can be generated during oxidative stress, and it is able to attack DNA, protein thiol groups, and membrane lipids (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”