Cr(III)-Mediated Hydroxyl Radical Generation via Haber-Weiss Cycle

Details

• Personal Author:
  Castranova, Vincent ; Gannett PM ; Leonard, Stephen S. ; Liu KJ ; Rojanasakul Y ; Shi X ; Vallyathan V ; Zang L
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chelating Agents Environmental Exposure Environmental Pollution Metals Neoplasms Occupational Exposure Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Cancer Carcinogenesis Carcinogenicity Chelates Chelating-agents Environmental-contamination Environmental-exposure Environmental-hazards Hydroxyl-groups Metal-compounds Occupational-exposure Pulmonary-system-disorders Respiratory-system-disorders

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• ISSN:
  0162-0134
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; New Hampshire ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 8 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  263-268
• Volume:
  69
• Issue:
  4
• NIOSHTIC Number:
  nn:20025468
• Citation:
  J Inorg Biochem 1998 Mar; 69(4):263-268
• Email:
  xas0@cdc.gov
• CAS Registry Number:
  Oxygen (CAS RN 7782-44-7)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Inorganic Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c1bf13d28f54a63d3dbc4280372d40d32140b42ca00819a3efbb1e030f2b2fd59efc1e3cca487c5af4c9d12c3d21a5b88fdae714295e6fc02d29d57956039273
• Download URL:
  https://stacks.cdc.gov/view/cdc/196819/cdc_196819_DS1.pdf
• File Type:
  [PDF - 149.20 KB ]