Chapter 20: Reactions of Singlet Oxygen with Nucleic Acids

The chapter is aimed at providing an updated overview of the main available data on the oxidation of nucleic acids by singlet oxygen (¹O₂). Mechanistic insights into the selective oxidative pathways of guanine, the predominant DNA and RNA target, were gained from detailed model studies. These have also allowed identification of spiroiminodihydantoin and minor 8-oxo-7,8-dihydroguanine as the main decomposition products of nucleosides and nucleotides. Evidence has been provided that the latter guanine oxidation product and thionucleobases are also highly reactive to singlet oxygen. The ¹O₂ oxidation of isolated and cellular DNA and RNA is much more specific giving rise almost exclusively to 8-oxo-7,8-dihydroguanine though the intermediacy of 4,8-endoperoxide that subsequently rearranges into easily reducible 8-hydroperoxyguanine. It was also shown that ¹O₂ is not able to induce significant levels of strand breaks and/or alkali-labile sites in cellular DNA upon exposure to a chemical source of singlet oxygen. UVA irradiation of cells and human skin is able to oxidatively damage nuclear DNA as inferred from the measurement of 8-oxo-7,8-dihydroguanine. This has been rationalized in terms of the predominant implication of ¹O₂ produced by type-II photosensitization mechanism over Fenton-type reactions.