Damage to plasmid DNA by singlet oxygen and its protection.

Singlet oxygen, generated by photoexcitation or by chemiexcitation, selectively reacts with the deoxyguanosine moiety in DNA (kq + kr about 5 x 10(6) M-1s-1). The oxidation products include 8-oxo-7,8-dihydroeoxyguanosine (8-oxodG; also called 8-hydroxydeoxyguanosine) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). Singlet oxygen also causes strand breaks in DNA, studied in plasmids and bacteriophages. The biological consequences include a loss of transforming activity as well as mutagenicity and genotoxicity. Employing shuttle vectors, it was shown that double-stranded vectors carrying singlet-oxygen-induced lesions seem to be processed in mammalian cells by DNA repair mechanisms efficient in preserving the biological activity of the plasmid but highly mutagenic in mammalian cells. Biological protection against singlet oxygen is afforded by quenchers, notably carotenoids (kq = 10(9) - 10(10) M-1s-1) and tocopherols. Whether this activity explains the protective effect of carotenoids on neoplastic transformation is still unknown.