Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice

Details

• Personal Author:
  Jacobs JM ; Kisin ER ; Murray AR ; Pounds JG ; Shvedova AA ; Teeguarden JG ; Varnum SM ; Waters, Kathy M. ; Webb-Robertson BJ ; Zanger RC
• Description:
  Reflecting their exceptional potential to advance a range of biomedical, aeronautic, and other industrial products, carbon nanotube (CNT) production and the potential for human exposure to aerosolized CNTs are increasing. CNTs have toxicologically significant structural and chemical similarities to asbestos (AB) and have repeatedly been shown to cause pulmonary inflammation, granuloma formation, and fibrosis after inhalation/instillation/aspiration exposure in rodents, a pattern of effects similar to those observed following exposure to AB. To determine the degree to which responses to single-walled CNTs (SWCNT) and AB are similar or different, the pulmonary response of C57BL/6 mice to repeated exposures to SWCNTs, crocidolite AB, and ultrafine carbon black (UFCB) were compared using high-throughput global high performance liquid chromatography fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR-MS) proteomics, histopathology, and bronchoalveolar lavage cytokine analyses. Mice were exposed to material suspensions (40 micrograms per mouse) twice a week for 3 weeks by pharyngeal aspiration. Histologically, the incidence and severity of inflammatory and fibrotic responses were greatest in mice treated with SWCNTs. SWCNT treatment affected the greatest changes in abundance of identified lung tissue proteins. The trend in number of proteins affected (SWCNT [376] > AB [231] > UFCB [184]) followed the potency of these materials in three biochemical assays of inflammation (cytokines). SWCNT treatment uniquely affected the abundance of 109 proteins, but these proteins largely represent cellular processes affected by AB treatment as well, further evidence of broad similarity in the tissue-level response to AB and SWCNTs. Two high-sensitivity markers of inflammation, one (S100a9) observed in humans exposed to AB, were found and may be promising biomarkers of human response to SWCNT exposure. [Description provided by NIOSH]
• Subjects:
  Asbestos Biological Factors Cytology Dust Environmental Monitoring Fibrosis Inorganic Chemicals Irritants Laboratories Lung Lung Diseases Microbiology Occupational Health Oxidants Particulate Matter Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Asbestos Author Keywords: Nanomaterials Biological-effects Biological-factors Cell-biology Cellular-reactions Exposure-assessment Exposure-levels Fibrogenicity Fibrous-bodies Fibrous-dusts Genotoxic-effects Inhalation-studies Laboratory-animals Lung-cells Lung-disorders Lung-irritants Microscopic-analysis Nanotechnology Oxidative-metabolism Oxidative-processes Particle-aerodynamics Particulates Proteomics Pulmonary-disorders Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Risk Assessment Statistical-analysis SWCNT

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Pennsylvania ; Washington ; 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:
  123-135
• Volume:
  120
• Issue:
  1
• NIOSHTIC Number:
  nn:20038398
• Citation:
  Toxicol Sci 2011 Mar; 120(1):123-135
• Email:
  justin.teeguarden@pnl.gov
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Carbon (CAS RN 7440-44-0) ; Carbon black (CAS RN 1333-86-4) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicological Sciences
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:80e8b9101d0d2134d2215e5f6d7f10748363bf4806f48a8256897a5a0223645bd2cfb7d8452999b83c18b3f2d2d42e74ebc84ffec805095308940e7e5edd3dee
• Download URL:
  https://stacks.cdc.gov/view/cdc/192118/cdc_192118_DS1.pdf
• File Type:
  [PDF - 803.07 KB ]