The Role of Hydroxyl Radical as a Messenger in Cr(VI)-Induced p53 Activation

Details

• Personal Author:
  Ding M ; Leonard, Stephen S. ; Shi X ; Wang S ; Ye J
• Description:
  The present study investigates whether reactive oxygen species (ROS) are involved in p53 activation, and if they are, which species is responsible for the activation. Our hypothesis is that hydroxyl radical (OH) functions as a messenger for the activation of this tumor suppressor protein. Human lung epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as the source of ROS due to its ability to generate a whole spectrum of ROS inside the cell. Cr(VI) is able to activate p53 by increasing the protein levels and enhancing both the DNA binding activity and transactivation ability of the protein. Increased cellular levels of superoxide radicals (O(2)(-).), hydrogen peroxide (H(2)O(2)), and OH radicals were detected on the addition of Cr(VI) to the cells. Superoxide dismutase, by enhancing the production of H(2)O(2) from O(2)(-) radicals, increased p53 activity. Catalase, an H(2)O(2) scavenger, eliminated OH radical generation and inhibited p53 activation. Sodium formate and aspirin, OH radical scavengers, also suppressed p53 activation. Deferoxamine, a metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable of generating radicals from H(2)O(2) NADPH, which accelerated the one-electron reduction of Cr(VI) to Cr(V) and increased OH radical generation, dramatically enhanced p53 activation. Thus OH radical generated from Cr(VI) reduction in A549 cells is responsible for Cr(VI)-induced p53 activation. [Description provided by NIOSH]
• Subjects:
  Antioxidants Carcinogens Chelating Agents Lung Neoplasms Occupational Health Peroxides Respiratory System Safety
• Keywords:
  Antioxidation Author Keywords: Cr(VI) Carcinogenesis Carcinogenesis Carcinogenicity Chelates Chelating Agents Lung Cells Proteins Reactive Oxygen Species Sodium Compounds Tumors

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• ISSN:
  0363-6143
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  279
• Issue:
  3
• NIOSHTIC Number:
  nn:20020846
• Citation:
  Am J Physiol Cell Physiol 2000 Sep; 279(3):C868-C875
• Contact Point Address:
  X. Shi, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505
• Email:
  xas0@cdc.gov
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1) ; Sodium (CAS RN 7440-23-5)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Cell Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:baf001b71661673d4ee0af18489e24cf0adf021c968c9ce71d4dcf7b8245aa2a62119ccb519ea0d40f4326d689ad619e93615a85b4a11bed8f26d3ac4b9d0066
• Download URL:
  https://stacks.cdc.gov/view/cdc/198506/cdc_198506_DS1.pdf
• File Type:
  [PDF - 333.31 KB ]