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.