Involvement of Vanadate-Mediated Reactive Oxygen Species in the Activation of Transcription Factor AP-1

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• Personal Author:
  Castranova, Vincent ; Colburn NH ; Ding M ; Leonard, Stephanie ; Li JJ ; Shi X ; Vallyathan V ; Ye JP
• Description:
  Previous studies from our laboratory have suggested a central role for reactive oxygen species (ROS) in the pathogenesis of occupational lung diseases. Environmental and occupational exposure to vanadium is common and is linked to an increased incidence of lung cancer. We hypothesized that the carcinogenicity of vanadium may be associated with its ROS-generating potential leading to activation of the transcription factor activator protein-1 (AP-1). In the present study, we investigated the activation of AP-1 with vanadate using mouse epidermal cells (JB6 p+) stably transfected with AP-1 luciferase reporter plasmid. This resulted in a dose dependent transactivation of AP-1, which was inhibited by SOD and catalase. Sodium formate, a specific OH scavenger, did not inhibit vanadate-induced AP-1 activation, whereas NADPH enhanced AP-1 activation. An antioxidant, N-acetyl-cysteine, decreased the activation, further showing that vanadate induced AP-1 activation is involved in redox reactions. Calphostin C, a specific inhibitor of protein kinase C (PKC), inhibited the activation of AP-1, demonstrating that PKC is involved in the cell signal cascades leading to vanadate-induced AP-1 activation. Electron spin resonance (ESR) measurements showed that JB6 p+ cells are able to reduce vanadate to vanadium (IV) in the presence of NADPH. Molecular oxygen was consumed during the vanadate reduction process to generate 028. SOD inhibited the ESR spin adduct signal, further demonstrating the generation of 028 in the cellular reduction of vanadate. These results provide support for a model in which vanadium, like other classes of tumor promoters (e.g., phorbol esters), transactivates AP-1-dependent gene expression. In the case of vanadium, the AP-1 transactivation is dependent on the generation of 02 and H202 but not OH. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Carcinogens Environmental Monitoring Hazardous Substances Laboratories Metals Neoplasms Occupational Health Respiratory Tract Diseases Safety Vanadium Compounds

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• Keywords:
  Analytical-methods Analytical-processes Animal-studies Cancer Carcinogenesis Carcinogenicity Exposure-assessment Laboratory-animals Metal-compounds Metal-oxides Pulmonary-system-disorders Respiratory-system-disorders Statistical-analysis Toxic-effects Toxins Vanadium-compounds

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• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  159
• Issue:
  3
• NIOSHTIC Number:
  nn:20028108
• Citation:
  Am J Respir Crit Care Med 1999 Mar; 159(3)(Suppl):A287
• CAS Registry Number:
  Sodium formate (CAS RN 141-53-7) ; Vanadium (CAS RN 7440-62-2)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4ebc9f813f1f34dee1113754f702dd0a3f754e124c8559a37e1a5c4fb82ee02b0101761d3c8d7eb87508e524168459bbcd9602aabfdde67fcd31f36eca90d577
• Download URL:
  https://stacks.cdc.gov/view/cdc/189780/cdc_189780_DS1.pdf
• File Type:
  [PDF - 338.27 KB ]