Synthesis of Cr(IV)-GSH, Its Identification and Its Free Hydroxyl Radical Generation: A Model Compound for Cr(VI) Carcinogenicity

Details

• Personal Author:
  Dalal NS ; Liu KJ ; Shi X
• Description:
  Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as an intermediate, toxic, carcinogenic species, but direct chemical evidence has been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr and few Cr(IV)-based compounds are known that can be used as a model compound containing a biological ligand. This study reports the isolation of such a stable Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits G = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in the powder form. Magnetic susceptibility measurements showed that the compound has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced it, indicating that the.OH radical was generated via a Fenton-like reaction, H2O2 being generated as an intermediate in the reduction of molecular oxygen. Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a deferoxamine-derived free radical was generated as shown by EPR measurements. The results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)-induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study the role of Cr(IV) in this mechanism. [Description provided by NIOSH]
• Subjects:
  Animals Carcinogens Dust Laboratories Metals Metals, Heavy Neoplasms Occupational Health Safety
• Keywords:
  Animal-studies Cancer-rates Carcinogenesis Heavy-metals Hydroxylation-reactions Laboratory-animals Metal-compounds Metal-dusts Metallic-compounds Metallic-dusts
• ISSN:
  0006-291X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Florida ; New Hampshire ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 4 ; 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:
  54-58
• Volume:
  235
• Issue:
  1
• NIOSHTIC Number:
  nn:20033936
• Citation:
  Biochem Biophys Res Commun 1997 Jun; 235(1):54-58
• Contact Point Address:
  X. Shi, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505
• CAS Registry Number:
  Chromic trioxide (CAS RN 1333-82-0) ; Chromium(6+) (CAS RN 18540-29-9)
• Federal Fiscal Year:
  1997
• Peer Reviewed:
  True
• Source Full Name:
  Biochemical and Biophysical Research Communications
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f40e672788fdf435bded4c8cf9b9c69ba0e0ae3d19a6b67962e37339cc459893829497143ac904597c8596bf30f7c1550e23ef54a6b47c90882130ca60660806
• Download URL:
  https://stacks.cdc.gov/view/cdc/189334/cdc_189334_DS1.pdf
• File Type:
  [PDF - 81.40 KB ]