DNA cleavage by hydroxyl radicals generated in a vanadyl ion-hydrogen peroxide system.
Vanadyl ion (+4 oxidation state) has been shown to be an effective agent for chemoprotection of cancers in animals. For understanding the mechanism, distribution of vanadium was studied. More vanadium was found to accumulate in the nuclei of the liver of rats when it was given as vanadyl sulfate than when it was given as sodium vanadate (+5 oxidation state). The reactivity of vanadyl ion with DNA was investigated by the DNA cleavage technique and the reaction mechanism by ESR spectroscopy. Incubation of double-strand DNA with vanadyl ion and hydrogen peroxide resulted in marked concentration- and pH-dependent DNA cleavage. Studies by the ESR spin-trap method demonstrated that hydroxyl radicals are generated during the reactions of vanadyl ion with hydrogen peroxide. Thus the antineoplastic action of vanadyl ion is proposed to be due to DNA cleavage by hydroxyl radicals generated in the cells.
Sakurai
H
H
Kyoto Pharmaceutical University, Japan.
Nakai
M
M
Miki
T
T
Tsuchiya
K
K
Takada
J
J
Matsushita
R
R
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003497:Cyclic N-Oxides; D004269:DNA, Bacterial / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide; D006878:Hydroxides; D017665:Hydroxyl Radical; D008099:Liver / Q000378:metabolism*; D008297:Male; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014639:Vanadium / Q000493:pharmacokinetics*; D017968:Vanadium Compounds
D003497:Cyclic N-Oxides; D004269:DNA, Bacterial; D005609:Free Radicals; D006878:Hydroxides; D013113:Spin Labels; D017968:Vanadium Compounds; D014639:Vanadium; D017665:Hydroxyl Radical; C034028:vanadyl sulfate; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D006861:Hydrogen Peroxide