137608-88-9Relevant articles and documents
Photooxiation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by thermally generated triplet-excited ketones from 3-(hydroxymethyl)-3,4,4-trimethyl-1,2-dioxetane and comparison with type I and type II photosensitizers
Adam, Waldemar,Saha-M?ller, Chantu R.,Sch?nberger, André
, p. 9233 - 9238 (1996)
Calf thymus DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were photooxidized in the dark by triplet-excited ketones generated in the thermal decomposition of 3-(hydroxymethyl)-3,4,4-trimethyl-1,2-dioxetane (HTMD). The oxidation of DNA led to 8-oxodGuo and the type I photooxidation product 2,2-diamino[2-deoxy-β-D-erythro-pentofuranosyl)-4-amino]-5(2H)-oxazol one (oxazolone). While the yield of oxazolone progressively increased, 8-oxodGuo was substantially consumed in DNA on successive exposure to HTMD. The oxidation of authentic 8-oxodGuo by HTMD and established photosensitizers such as benzophenone (mainly type I) and Rose Bengal (predominantly type II) was studied in detail in regard to the concentration and time dependence and the influence of D2O versus H2O. The singlet-oxygen-derived 4R* and 4S* diastereomers of 4-hydroxy-8-oxo-4,8-dihydro-2'-deoxyguanosine (4-HO-8-oxodGuo) and oxazolone were the major products. A substantial kinetic D2O effect (ca. 10-fold) in the Rose Bengal-photosensitized degradation of 8-oxodGuo unequivocally established that in this case singlet oxygen (type II photooxidation) is involved. However, the efficient formation of oxazolone by benzophenone as a characteristic type I photooxidant, as well as in the HTMD-mediated oxidation (predominantly type I), and the fact that these processes exhibit a negligible D2O effect provide cogent experimental evidence for an electron or hydrogen atom transfer mechanism (type I photooxidation) in the oxidative degradation of 8-oxodGuo into oxazolone. The unprecedented observation that comparable product ratios of 4-HO-8-oxodGuo and oxazolone were obtained in the 8-oxodGuo oxidations, irrespective of whether Rose Bengal as a typical type II photooxidant or benzophenone as an established type I photooxidant was employed, is presumably due to electron-transfer chemistry of 1O2 with the easily oxidized 8-oxodGuo in view of its low oxidation potential. This nicely accounts for the fact that the primary oxidation product 8-oxodGuo, which serves as an important monitor of oxidative genotoxicity, may not accumulate appreciably in the photooxidation of DNA.
Reaction of Singlet Oxygen with 2'-Deoxyguanosine and DNA. Isolation and Characterization of the Main Oxidation Products
Ravanat, Jean-Luc,Cadet, Jean
, p. 379 - 388 (1995)
The reaction of singlet molecular oxygen with 2'-deoxyguanosine and DNA was studied. Emphasis was placed on the identification and characterization of the main methylene blue mediated type II (singlet oxygen) oxidation products of 2'-deoxyguanosine and its corresponding 3',5'-di-O-acetylated derivative. Two major oxidation products of 2'-deoxyguanosine were isolated and characterized by mass spectrometry analysis and extensive 1H and 13C NMR measurements as the two 4R* and 4S* diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine. The addition of 1O2 was also found to occur to the base moiety of the corresponding 3',5'-di-O-acetylated derivative. Methylene blue mediated photosensitization of 2'-deoxygunosine led also to the production of 7,8-dihydro-8-oxo-2'-deoxyguanosine, but in a relatively lower yield with respect to the two above diastereomers. The participation of singlet oxygen in the mechanism of formation of these oxidation products was confirmed. A reasonable mechanism involving the transient formation of an unstable endoperoxide produced through a Diels-Alder 1,4-cycloaddition of singlet oxygen to the purine ring is suggested. Quantitative analysis allowed us to demonstrate that the two diastereomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine are the main singlet oxygen oxidation products of the guanine moiety within nucleosides, whereas 7,8-dihydro-8-oxoguanine was found to be the major 1O2 oxidation product of guanine in double-stranded DNA.
Hydroxyl radical-induced degradation of 2′-deoxyguanosine under reducing conditions
Douki, Thierry,Spinelli, Sandrine,Ravanat, Jean-Luc,Cadet, Jean
, p. 1875 - 1880 (1999)
Addition of hydroxyl radical to the base moiety of 2′-deoxyguanosine (dGuo) leads to the formation of two main radicals exhibiting oxidising and reducing properties, respectively. The oxidising radical reacts with oxygen to yield 2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]oxazol-5(2H)-one (oxazolone) as the final product. The reducing radical is either preferentially oxidised into 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) or reduced into a 2,6-diamino-4-hydroxy-5-formamidopyrimidine derivative (FapydGuo) depending on conditions. We report here that the presence of reducing compounds (ascorbate or cysteine) strongly modifies the distribution of modified nucleosides upon γ irradiation of an aerated aqueous solution of dGuo. The yield of oxazolone decreases while that of 8-oxodGuo and FapydGuo increases. This was explained by the reduction of the oxidising radical which prevents the occurrence of the restitution of dGuo through a reaction between the oxidising and the reducing purine radicals. The study was extended to the decomposition of dGuo upon photochemical release of .OH by N-hydroxypyrimidine-2-thione (HPT). The analysis of the base modification products of dGuo induced by the latter system showed that HPT exhibits reducing properties and cannot be used as a pure photochemical source of ?OH radical.
Identification of the α and β anomers of 1-(2-deoxy-D-erythro- pentofuranosyl)-oxaluric acid at the site of riboflavin-mediated photooxidation of guanine in 2′-deoxyguanosine and thymidylyl-3′-5′- deoxyguanosine
Buchko, Garry W.,Cadet, Jean
, p. 191 - 199 (2008/02/05)
Products of riboflavin-mediated photosensitization of 2′- deoxyguanosine (dG) and thymidylyl-(3′-5′)-2′-deoxyguanosine (TpdG) by 350-nm light in oxygen-saturated aqueous solution have been isolated and identified as 1-(2-deoxy-β-erythro-pentofuranosyl) oxaluric acid (β-dOx) and thymidylyl-(3′-5′)-1-(2-deoxy-β-D-erythro- pentofuranosyl) oxaluric acid (Tpβ-dOx), respectively. In aqueous solution the modified β-deoxyribonucleoside is slowly converted to the α-anomer, generating α-dOx and Tpα-dOx. These modified nucleosides and dinucleoside monophosphates have been isolated by HPLC and characterized by proton and carbon NMR spectroscopy, fast atom bombardment mass spectrometry, and enzymatic analyses. Both α-dOx and Tpα-dOx slowly convert back into the modified β-deoxyribonucleoside, indicating that the furanosidic anomers are in dynamic equilibrium. Relative to TpdG, the rate of hydrolysis of Tpβ-dOx and Tpα-dOx by spleen phosphodiesterase is greatly reduced. Hot piperidine (1.0 M, 90°C, 30 min) destroys Tpβ-dOx and Tpα-dOx. Riboflavin-mediated photosensitization of TpdG in D 2O instead of H2O has no detectable effect on the yield of Tpβ-dOx, suggesting that oxaluric acid is generated through a Type-I reaction mechanism, likely through the intermediary on initially generated 8-oxo-7,8-dihydro-2′-deoxyguanosine.
