Comparison of oxidation products from DNA components by gamma-irradiation and Fenton-type reactions.
The four 2'-deoxyribonucleosides were gamma-irradiated or were aerobically treated with Fenton-type-reagents, Fe(II)-EDTA or a renal carcinogen Fe(II)-nitrilotriacetic acid (NTA) under the neutral conditions. The reaction mixtures were immediately analyzed by reverse-phase HPLC. Major products detected were 2-hydroxydeoxyadenosine (2-OH-dA), 8,5'-cyclodeoxyadenosine (cyclo-dA), 8-hydroxydeoxyadenosine (8-OH-dA). 5-formyldeoxyuridine (5-CHO-dU), 5-hydroxydeoxycytidine (5-OH-dC), 8-hydroxydeoxyguanosine (8-OH-dG), 8,5'-cyclodeoxyguanosine (cyclo-dG), and glyoxal and its adduct with dG. Ratio of these oxidized products were dramatically changed depending upon the agents used. For example, 2-OH-dA was a modified nucleoside produced most efficiently by Fe(II)-EDTA, while 5-CHO-dU and 5-OH-dC were the major products by the Fe(II)-NTA treatment and gamma-irradiation, respectively. Glyoxal itself was estimated to be produced most frequently (13 folds of 8-OH-dG) when treated with Fe(II)-EDTA, but its formation was not detected by the treatment with Fe(II)-NTA or by gamma-irradiation. 8-OH-dA was not produced by Fe-EDTA or Fe-NTA but was produced by gamma-irradiation. In contrast, 2-OH-dA was not produced by gamma-irradiation. These results suggest that triphosphates of 2-OH-dA, cyclo-dA, 8-OH-dA, cyclo-dG, 5-CHO-dU, 5-OH-dC, and glyoxal-dG as well as 8-OH-dG may be produced in cells with different ratio by various types of oxidative stress and involved in mutagenesis and carcinogenesis.
Murata-Kamiya
N
N
Department of Health Policy and Management, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kamiya
H
H
Muraoka
M
M
Kaji
H
H
Kasai
H
H
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D009705:Nucleosides / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology*
C045076:Fenton's reagent; D009705:Nucleosides; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron