Size-Dependent Effects of Tungsten Carbide – Cobalt Particles on Oxygen Radical Production and Activation of Cell Signaling Pathways in Murine Epidermal Cells

Details

• Personal Author:
  Bowman L ; Castranova, Vincent ; Ding M ; Fadeel B ; Jiang B ; Kisin ER ; Leonard, Stephanie ; 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 nano-sized 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-kappaB, 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+/+ 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. Finally, co-incubation of the JB6+/+ cells with N-acetyl-cysteine decreased AP-1 activation and phosphorylation of ERKs, p38 kinase, and JNKs, thus suggesting that oxidative stress is involved in WC--Co-induced toxicity and AP-1 activation. [Description provided by NIOSH]
• Subjects:
  Carcinogens Free Radicals Metals Neoplasms Occupational Health Safety Skin
• Keywords:
  Author Keywords: Skin Cancer Free-radicals Nanoparticles Nanotechnology Signaling Pathway Transcription Factor Tungsten Carbide--cobalt
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  260-268
• Volume:
  241
• Issue:
  3
• NIOSHTIC Number:
  nn:20036048
• Citation:
  Toxicol Appl Pharmacol 2009 Dec; 241(3):260-268
• Contact Point Address:
  A.A. Shvedova, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Cobalt (CAS RN 7440-48-4) ; Tungsten (CAS RN 7440-33-7) ; Tungsten carbide (CAS RN 11130-73-7)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1eb4f452a572014e21d4de6b1b4573d33a0e4758d4702409c8879f17eb4c01f3cd59934d9e791de7243372bee2271e5baa473a07ce4f386820cbb6b4f3c11446
• Download URL:
  https://stacks.cdc.gov/view/cdc/187654/cdc_187654_DS1.pdf
• File Type:
  [PDF - 727.70 KB ]