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

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.