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Cr(III)-mediated hydroxyl radical generation via Haber-Weiss cycle.
Shi X; Leonard SS; Liu KJ; Zang L; Gannett PM; Rojanasakul Y; Castranova V; Vallyathan V
J Inorg Biochem 1998 Mar; 69(4):263-268
ESR spin trapping and HPLC were utilized to investigate Cr(III)-mediated hydroxyl radical (OH) generation via the following Haber-Weiss reactions in vitro: Cr(III)+O2->Cr(II)+O2, Cr(II)+H2O2 -> Cr(III)+ OH+OH-. Xanthine and xanthine oxidase were used as a source of superoxide (O2-) and H2O2. A mixture of xanthine and xanthine oxidase in the presence of the spin trapping agent, 5,5-dimethyl-pyrroline N-oxide (DMPO), generated DMPO/O2-. Addition of Cr(III) to this mixture generated DMPO/OH. Catalase partially inhibited DMPO/OH formation, while the combination of catalase and superoxide dismutase (SOD) completely blocked the generation of DMPO/OH. The reaction of Cr(III) with H2O2, itself, also generated DMPO/OH. This H2O2 enhanced DMPO/OH formation was significantly increased in the presence of xanthine, and xanthine oxidase. Metal chelators, deferoxamine, 1,10-deferoxamine and EDTA, decreased Cr(III)-dependent OH generation. Parallel ESR spin trapping measurements were carried out using Cr(VI). Although Cr(III) generated OH via a Haber-Weiss cycle, the relative yield of the OH formation was comparable to that of a Fe(II)-mediated one but lower than that generated by a Cr(VI)-mediated Haber-Weiss cycle. HPLC measurements also show that the OH radical generated via a Cr(III)-mediated Haber-Weiss reaction was capable of causing 2'-deoxyguanosine (dG) hydroxylation to generate 8-hydroxyl-2'-deoxyguanosine (8-OHdG). The relative yield of 8-OHdG formation correlated with the generation of OH as measured by ESR spin trapping. The results suggest that Cr(III)-mediated OH radical generation may contribute to the mechanism of Cr(III)- and Cr(VI)-induced carcinogenesis.
Hydroxyl-groups; Metals; Metal-compounds; Chelating-agents; Chelates; Carcinogenesis; Carcinogenicity; Carcinogens; Environmental-hazards; Environmental-contamination; Environmental-exposure; Occupational-exposure; Cancer; Respiratory-system-disorders; Pulmonary-system-disorders
Issue of Publication
Journal of Inorganic Biochemistry
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