Oxaluric acid as the major product of singlet oxygen-mediated oxidation of8-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 i ts 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 ox idation 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 fo und to be the predominant product of the reaction. Insights in the mechanis tic pattern of oxaluric acid formation were gained from isotopic labeling e xperiments in association with mass spectrometry measurements. It was found that oxaluric acid is formed via an oxidized guanidinohydantoin intermedia te, arising from the likely degradation of a transient 5-hydroperoxide. Two subsequent hydrolytic steps that are accompanied by the release of guanidi ne are likely to be involved in the formation of oxaluric acid.