Vanadium(IV) causes 2'-deoxyguanosine hydroxylation and deoxyribonucleic acid damage via free radical reactions.
Vanadium(IV) caused molecular oxygen dependent 2'-deoxyguanosine (dG) hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15-minute incubation of 1.0 mM dG and 1.0 mM VOSO4 (vanadium(IV)) in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31 percent. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Diethylenetriaminepentaacetic acid (DTPA) and deferoxamine blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen dependent deoxyribonucleic acid (DNA) strand breaks in a pattern similar to that observed for dG hydroxylation. Reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA strand breaks. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks.
Shi
X
X
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
Wang
P
P
Jiang
H
H
Mao
Y
Y
Ahmed
N
N
Dalal
N
N
D002614:Chelating Agents / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation; D010545:Peroxides / Q000378:metabolism; D014639:Vanadium / Q000633:toxicity*; D020122:tert-Butylhydroperoxide
D002614:Chelating Agents; D010545:Peroxides; D014639:Vanadium; D017665:Hydroxyl Radical; D004247:DNA; D020122:tert-Butylhydroperoxide; D003849:Deoxyguanosine