Size-Dependent Effects of Tungsten Carbide-Cobalt Particles on Induction of Oxidative Stress and Activation of Cell Signaling Pathways In Vitro

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Fadeel B ; Jiang B ; Kisin ER ; Leonard, Stephen S. ; Lu Y ; Murray AR ; Shvedova AA ; Vallyathan V ; Zhao J
• Description:
  Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC) (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially carcinogenic to humans. However, no comparison of the adverse effects of nanosized WC-Co particles is available to date. In the present study, we compared the ability of nano- and fine-sized WC-Co particles to form free radicals, and propensity to activate the transcription factors, AP-1 and NF-êB, along with stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a mouse epidermal cell line (JB6 P+). Our results demonstrated that nano-WC-Co generated a higher level of hydroxyl radicals, induced greater oxidative stress, as evidenced by a decrease of GSH levels, and caused faster JB6 P+ cell growth/proliferation than observed after exposure of cells to fine-WC-Co. In addition, nano-WC-Co activated AP-1 and NF-kappaB more efficiently in JB6 P+ cells, as compared to fine-WC-Co. Experiments using AP-1-luciferase reporter transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine-sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. Overall, these findings demonstrated that both fine- and nano-sized WC-Co induce ROS generation, cell proliferation, and activation of specific cell signaling pathways. These studies also underscore that size is a critical factor in assessment of toxicological and biological responses of WC-Co materials [Description provided by NIOSH]
• Subjects:
  Chemistry Environmental Monitoring Hazardous Substances Hypersensitivity Laboratories Microbiology Occupational Health Oxidants Particulate Matter Safety
• Keywords:
  Biological-effects Cell-biology Cellular-reactions Chemical-hypersensitivity Chemical-properties Exposure-assessment Exposure-levels Exposure-methods Laboratory-animals Laboratory-testing Microscopic-analysis Molecular-biology Oxidation Oxidative-metabolism Oxides Particulate-dust Particulates Toxic-effects Toxic-materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 8 ; Pennsylvania ; Utah ; 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:
  59
• Volume:
  114
• Issue:
  1
• NIOSHTIC Number:
  nn:20036602
• Citation:
  Toxicologist 2010 Mar; 114(1):59
• CAS Registry Number:
  Tungsten (CAS RN 7440-33-7)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ebb9748d36cc365caad71394321c32c75b59755084da826199d074c9db28347df232c8c0c49ba8143ea9f543a9b6d18a1d30275fd4f1127883c150d5eeb04b94
• Download URL:
  https://stacks.cdc.gov/view/cdc/187959/cdc_187959_DS1.pdf
• File Type:
  [PDF - 736.47 KB ]