Biological consequences associated with DNA oxidation mediated by singlet oxygen.

Singlet oxygen is a major oxidative species that can be generated by numerous biological processes such as photosensitization. This oxidant can react with deoxyguanosine and with guanine in deoxyribonucleic acid (DNA) leading to the induction of at least four different reaction products such as 4,8-dihydro-4-hydroxy-8-oxodeoxyguanosine and 7,8-dihydro-8-oxodeoxyguanosine. The induction of true single-stranded breaks in the oxidated DNA is still a matter of controversy and is not yet clearly established. This paper focuses mainly on several biological consequences which can be associated with the induction of DNA lesions by singlet oxygen. Oxidated DNA loses its transformation efficiency probably because unrepaired lesions can partially inhibit DNA replication. Mutagenesis is one of the main effects induced by guanine oxidation products. Molecular analysis of mutated genes reveals that G to T transversions are the most frequent mutations; these are probably introduced in DNA by misincorporation of deoxyadenosine monophosphate (dAMP) opposite to the lesion. Efficient repair of these oxidated guanine residues can take place via specific glycosylase, endonuclease or the SOS network. However, the data concerning the toxicity of singlet oxygen for eukaryotic cells are not frequent enough in the literature to draw a clear picture of the effects of this activated species in several biologically revelant phenomena.