Role of molecular oxygen in the generation of hydroxyl and superoxide anion radicals during enzymatic Cr(VI) reduction and its implication to Cr(VI)-induced carcinogenesis.

Abstract

Electron spin resonance (ESR) spin trapping measurements provide evidence for the generation of hydroxyl radicals (*OH) in the reduction of Cr(VI) by glutathione reductase (GSSG-R) in the presence of NADPH as a cofactor. Catalase inhibited the *OH generation, while the addition of H2O2 enhanced it, indicating that the *OH radical generation involves a Fenton-like reaction. The metal chelator, deferoxamine, inhibited the *OH generation with a concomitant generation of a deferoxamine nitroxide radical. EDTA and 1,10-phenanthroline also inhibited the *OH generation. Experiments performed under argon atmosphere decreased the yield of the *OH formation, showing that molecular oxygen plays a critical role. ESR spin trapping and measurements of fluorescence change of scopoletin in the presence of horseradish peroxidase show that reduction of Cr(VI) by GSSG-R/NADPH generates superoxide anion radicals (O2*-) as well as H2O2. It can be concluded that *OH radical is generated by the reaction of H2O2 with Cr(V), which is produced by enzymatic one-electron reduction of Cr(VI). H2O2 is produced by the reduction of molecular oxygen via O2*- as an intermediate. The *OH radicals generated by these reactions are capable of causing DNA strand breaks, which can be inhibited by catalase, formate, and experiments performed under argon.

• Authors: S Leonard, S Wang, L Zang, V Castranova, V Vallyathan, X Shi
• Journal: Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer (J Environ Pathol Toxicol Oncol) Vol. 19 Issue 1-2 Pg. 49-60 ( 2000) ISSN: 0731-8898 [Print] United States
• PMID: 10905508 (Publication Type: Journal Article)

Chemical References

• Carcinogens
• Chelating Agents
• Chromium
• Superoxides
• Hydroxyl Radical
• NADP
• DNA
• Hydrogen Peroxide
• Glutathione Reductase
• Deferoxamine
• Oxygen

Topics

• Carcinogenicity Tests
• Carcinogens
• Chelating Agents (pharmacology)
• Chromium (chemistry, toxicity)
• DNA (drug effects, metabolism)
• DNA Damage
• Deferoxamine (pharmacology)
• Electron Spin Resonance Spectroscopy (methods)
• Glutathione Reductase (chemistry)
• Hydrogen Peroxide (chemistry, toxicity)
• Hydroxyl Radical (chemistry, toxicity)
• NADP (chemistry)
• Oxidation-Reduction
• Oxygen (chemistry)
• Oxygen Consumption
• Superoxides (chemistry, toxicity)