| Vanadium Distribution in Rats and DNA Cleavage by Vanadyl Complex: Implication for Vanadium Toxicity and Biological Effects Environ Health Perspect Key words: vanadium, distribution, neutron activation analysis, electron spin resonance (ESR), DNA cleavage, hydroxyl radicals, spin trapping
This paper was presented at the Second International Meeting on Molecular Mechanisms of Metal Toxicity and Carcinogenicity held 10-17 January 1993 in Madonna di Campiglio, Italy.
Address correspondence to Dr. Hiromu Sakurai, Department of Analytical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607, Japan.
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Vanadium ion is toxic to animals. However, vanadium is also an agent used for chemoprotection against cancers in animals. To understand both the toxic and beneficial effects we studied vanadium distribution in rats. Accumulation of vanadium in the liver nuclei of rats given low doses of compounds in the +4 or +5 oxidation state was greater than in the liver nuclei of rats given high doses of vanadium compounds or the vanadate (+5 oxidation state) compound. Vanadium was incorporated exclusively in the vanadyl (+4 oxidation state) form. We also investigated the reactions of vanadyl ion and found that incubation of DNA with vanadyl ion and hydrogen peroxide (H2O2) led to intense DNA cleavage. ESR spin trapping demonstrated that hydroxyl radicals are generated during the reactions of vanadyl ion and H2O2. Thus, we propose that the mechanism for vanadium-dependent toxicity and antineoplastic action is due to DNA cleavage by hydroxyl radicals generated in living systems. -- Environ Health Perspect 102(Suppl 3) :35-36 (1994) . Key words: vanadium, distribution, neutron activation analysis, electron spin resonance (ESR) , DNA cleavage, hydroxyl radicals, spin trapping
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