Tungsten Carbide-Cobalt Particles Activate Nrf2 and Its Downstream Target Genes in JB6 Cells Possibly by ROS Generation

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Shi X ; Zhang XD ; Zhao J
• Description:
  Hard metal consisting of a mixture of tungsten carbide (WC) and metallic cobalt (Co) was evaluated as a possible carcinogen in humans by IARC in 2003. Studies have suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) constitutes one of the chemical-sensing and transcription systems that play an essential role(s) in chemical toxicity, carcinogenesis, and pathological processes. To elucidate the mechanisms of health hazards of WC-Co, effects of nano-WC-Co particles on Nrf2 signaling pathway were investigated in the present study in a JB6 cell line. After a 5 h treatment with nano-WC-Co particles, Nrf2 was released from Keap1 in the cytoplasm and translocated into the nucleus. Enzymatic activities of Nrf2 target genes, including glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), increased at 24 and 48 h after the treatment. Studies using reactive oxygen species (ROS) sensitive dyes indicated that ROS were produced in nano-WC-Co particle-treated cells. Pretreatment of the cells with catalase, but not sodium formate, resulted in a signifi cant inhibitory effect on nano-WC-Co particle-induced Nrf2 target gene activation. These fi ndings suggest that activation of Nrf2 and its downstream genes may be initiated by ROS generation, and ROS may act as a major contributor in nano-WC-Co particle-induced adverse health effects. [Description provided by NIOSH]
• Subjects:
  Antioxidants Carcinogens Metals Mutagens Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Tungsten Carbide-cobalt (WC-Co) Cancer Carcinogenesis Mutation Nanoparticles Nanotechnology Nrf2 Nuclear Factor Erythroid 2-related Factor 2 Reactive Oxygen Species ROS Tungsten-compounds

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• ISSN:
  0731-8898
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Kentucky ; 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:
  31-40
• Volume:
  29
• Issue:
  1
• NIOSHTIC Number:
  nn:20036699
• Citation:
  J Environ Pathol Toxicol Oncol 2010 Jan; 29(1):31-40
• Contact Point Address:
  Min Ding, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  mid5@cdc.gov
• CAS Registry Number:
  Cobalt (CAS RN 7440-48-4) ; Tungsten carbide (CAS RN 11130-73-7)
• Federal Fiscal Year:
  2010
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Environmental Pathology, Toxicology, and Oncology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f6f68a8f5c735957bdc0cbb0f4a280bbb6cc395ddc57264e576a1c9b5464d2dae07e7d5a488e22cadf2192d0e1c1348c0a156ef3274c94926fe398481295fd20
• Download URL:
  https://stacks.cdc.gov/view/cdc/188019/cdc_188019_DS1.pdf
• File Type:
  [PDF - 556.36 KB ]