Molecular Mechanism of Cr(VI)-Induced Carcinogenesis

Details

• Personal Author:
  Castranova, Vincent ; Shi X ; Vallyathan V
• Description:
  We hypothesize that reduction of Cr(VI) to its low oxidation states, Cr(V) and Cr(IV), is an important step in the mechanism of Cr(VI)-induced carcinogenesis. These chromium intermediates are able to generate reactive oxygen species (ROS), which initiate Cr(VI)-induced carcinogenesis. Through free radical reactions, Cr(VI) can activate multiple carcinogenic processes. (1) Cr(VI) causes activation of nuclear transcription factor kappa B (NF -KB). Among ROS, hydroxyl radicals (OH) are responsible for Cr(VI)-induced NF-KB activation. (2) Cr(VI) is able to activate activator protein-1 (AP-l). (3) Cr(VI) causes p53 activation and OH radicals function as messengers for the activation of this tumor suppressor protein. (4) Cr(VI) is capable of inducing apoptosis via both p53 and ROS-mediated reactions. (5) Cr(VI) causes over-expression of oncogenes (jun-B and raf), up-regulation of antioxidants (glutathione peroxidase), activation of certain enzymes involved in mitogen-activated protein kinase (MAP kinase) signal pathways (MAPKAP kinase), stimulation of enzymes involved in cell cycle control and checkpoint mechanisms (checkpoint suppressor 1), and activation of enzymes responsible for Cr(VI) reduction, such as NAD(P)H dependent dihydrolipoamide dehydrogenase. Cr(VI)-containing compounds are considered to be well established carcinogens (1). They are potent inducers of tumors in experimental animals and active agents in causing DNA damage such as DNA strand breakage. We have hypothesized that reduction of Cr(VI) to its low oxidation states, Cr(V) and Cr(IV), is an important step (2). These chromium intermediates are able to generate ROS, which initiate Cr(VI)-induced carcinogenesis. This article summarizes our studies on Cr(VI) reduction and related free radical generation and the role of free radical reactions in various potential mechanisms for the initiation of carcinogenesis induced by this metal. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Carcinogens Chromium Free Radicals Laboratories Metals Occupational Health Safety
• Keywords:
  Animal Studies Carcinogenesis Carcinogenicity Chromium Compounds Free Radical Generation Free Radicals Laboratory Animals Oncogenesis Oncogenic Agents Oncogenicity
• Publisher:
  John Libbey Eurotext
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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
• Pages in Document:
  110-112
• Volume:
  6
• NIOSHTIC Number:
  nn:20021064
• Citation:
  Metal ions in Biology and Medicine, 2000, J. A. Cantano, P. Collery, G. Vernet, R. B. Finkelman, H. Gibb, J. C. Etienna, eds. Paris, France: John Libbey Eurotext, 2000 Jan; 6:110-112
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3)
• Editor(s):
  Cantano JA; Collery P; Vernet G; Finkelman RB; Gibb H; Etienna JC
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  Metal ions in Biology and Medicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:23a0bd29f1988df94ae39c99e8bb3b19932d1164e4206a86f51e9df0abf521a46816a3ce19724c42e28acbf3eb76e36d93731c3c7b37d877b1b0f76067820a27
• Download URL:
  https://stacks.cdc.gov/view/cdc/198630/cdc_198630_DS1.pdf
• File Type:
  [PDF - 142.83 KB ]