Induction of AP-1-MAPKs and NF-kB Signal Pathways by Tungsten Carbide-Cobalt Particles

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Kisin E ; Leonard, Stephanie ; Lu Y ; Murray A ; Shvedova A ; Vallyathan V ; Zhao J
• Description:
  Hard metal consists of a powder mixture of tungsten carbide (WC,85%) and metallic cobalt (Co,5-15%). WC-Co was evaluated as a probable carcinogen in humans by IARC in 2003. It is believed that the toxicity and carcinogenesis of WC-Co is associated with particle size. Although nanomaterials are currently being widely used in modern technology, there is a serious lack of information concerning human health effects and environmental implications of manufactured nanomaterials. In this report, we investigated the effects of nano- (40-80 nm) and fine (40 um) 85WC/15Co particles on AP-1-mitogen-activated protein kinase (MAPKs) and NF-kB signaling in mouse epidermal (JB6) cells. The results demonstrated that the induction of AP-1 activity by nano-WC-Co was 4-times higher than that stimulated by fine-WC-Co. Similar results were obtained for NF-kB induction. The induction of AP-1 and NF-kB activity in cultured cells was time and dose-dependent. The signal transduction pathways for AP-1 activation were also investigated and the results demonstrated that both nano- and fine-WC-Co stimulate MAPK family members, including extra-cellular signal-regulated protein kinase (ERKs), p38 kinase, and C-Jun N-terminal kinase (JNKs). The potency of nano-WC-Co on MAPKs stimulation was significantly higher than that for fine WC-Co. Electron spin resonance (ESR) studies indicated that nano-WC-Co generated more reactive oxygen species (ROS) than the fine particles when incubated with the cells. Study using ROS- sensitive dyes support the conclusion that ROS are generated by WC-Co-treated cells. N-Acetylcysteine, an antioxidant agent, decreased AP-1 activation and phosphorylation of ERKs, p38 kinase and JNKs, suggest the involvement of ROS in the mechanisms of WC-Co-induced AP-1 activation. These findings demonstrate that WC-Co induces NF-kB and AP-1-MAPKs activation, which may be mediated through ROS. The size of the particles plays a critical role in toxicity and carcinogenicity of the hard metal. [Description provided by NIOSH]
• Subjects:
  Antioxidants Laboratories Occupational Health Particulate Matter Safety Skin Skin Absorption Skin Diseases
• Keywords:
  Laboratory-animals Nanotechnology Particle-aerodynamics Particulate-dust Particulates Quantitative-analysis Skin-absorption Skin-disorders Skin-exposure Skin-irritants
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Montana ; OSHA Region 10 ; OSHA Region 8 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033582
• Citation:
  Toxicologist 2008 Mar; 102(1):212
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3866f711ff590d6cc9db9ec96ebc2b989e522e0048302757fe28bfddc4bbc710f1aa97a516a6c9ff570f62bbba4901a2e92c6c40d3cc42123ab2bf0ed165946d
• Download URL:
  https://stacks.cdc.gov/view/cdc/189090/cdc_189090_DS1.pdf
• File Type:
  [PDF - 7.82 MB ]