Formation of a diimino-imidazole nucleoside from 2'-deoxyguanosine by singlet oxygen generated by methylene blue photooxidation.
Singlet oxygen ((1)O(2)) is capable of inducing genotoxic, carcinogenic and mutagenic effects. It has previously been reported that the reaction of (1)O(2) with 2'-deoxyguanosine, which is a major target of (1)O(2) among the DNA constituents, leads to formation of various oxidized products including 8-oxo-7,8-dihydro-2'-deoxyguanosine and spiroiminodihydantoin, amino-imidazolone and diamino-oxazolone nucleosides. In addition to these products, we report that a novel diimino-imidazole nucleoside, 2,5-diimino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-2H,5H-imidazole (dD), is formed by reaction of 2'-deoxyguanosine with (1)O(2) generated by irradiation with visible light in the presence of methylene blue under aerobic conditions. Its identification is based on identical chromatographic and spectroscopic data with an authentic compound, which we recently isolated and characterised from the reaction mixture of 2'-deoxyguanosine with reagent HOCl and a myeloperoxidase-H(2)O(2)-Cl(-) system. The yield of dD was increased by D(2)O and decreased by azide. dD was not generated from 8-oxo-7,8-dihydro-2'-deoxyguanosine. These results indicate that dD is generated by (1)O(2) directly from 2'-deoxyguanosine, but not via 8-oxo-7,8-dihydro-2'-deoxyguanosine. dD may play a role in the genotoxicity of singlet oxygen in cells.
Suzuki
Toshinori
T
International Agency for Research on Cancer, 150 Cours Albert Thomas, F 69372 Cedex 08, Lyon, France.
Friesen
Marlin D
MD
Ohshima
Hiroshi
H
D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000737:chemistry*; D017666:Deuterium Oxide; D007093:Imidazoles / Q000737:chemistry; D008751:Methylene Blue / Q000737:chemistry; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry*; D019810:Sodium Azide; D013997:Time Factors
D007093:Imidazoles; D009705:Nucleosides; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D019810:Sodium Azide; D003849:Deoxyguanosine; D017666:Deuterium Oxide; D008751:Methylene Blue