Pathology-directed mass spectrometry determines proteomic differences associated with carbon nanotube exposure in the lung

Details

• Personal Author:
  Antonini JM ; Battelli LA ; Bishop L ; Boyce G ; Erdely A ; Kilby GW ; Salmen R ; Seeley EH ; Zeidler-Erdely PC
• Description:
  Multi-walled carbon nanotubes (MWCNT) have tremendous industry application however, their unique physicochemical properties may pose health risks after inhalation. For insight into the adverse mechanisms associated with MWCNT deposition in the lung, pathology-directed mass spectrometry profiling was used; a method to identify regionally-specific alterations in proteins, lipids, and metabolites. Mice were exposed by oropharyngeal aspiration to vehicle or MWCNT (10 or 40 ug). Lungs were perfused 24 h post-exposure, inflated with 50% OCT, snap frozen and sections collected on MALDI targets with a serial section stained with H&E. Areas of interest (alveolar and terminal bronchial areas, regions with MWCNT deposition, and regions in treated mice without MWCNT deposition; 50 um in diameter; n=15-20 per section per area) were annotated on H&E stained sections and matched digitally to the corresponding serial section for mass spectra collection to determine proteomic differences. Principal component analyses showed separation of sham from MWCNT-exposed animals and in treated mice in areas with and without deposition. Genetic algorithm classification models indicated spectral classification accuracies of 85% for control, 80% for MWCNT deposition, and 80% for treatment with no deposition. Spectral data (2-40 kDa) indicated numerous peaks separating areas of interest. For example, m/z 10165 and 12973 were increased in areas of MWCNT deposition whereas m/z 3954 was decreased as a result of exposure irrespective of deposition. Segregation was evident in the exposed group as areas without obvious deposition, which either showed no alteration compared to sham (m/z 9450) or the response was blunted compared to areas of obvious deposition (m/z 17097). This methodological approach not only reveals a dynamic range of alterations due to exposure but provides context regionally with respect to MWCNT deposition, thus providing insight into specific mechanisms of MWCNT-induced lung pathology. [Description provided by NIOSH]
• Subjects:
  Chemistry Energy Metabolism Environmental Monitoring Genetics Laboratories Lipids Lung Mass Spectrometry Occupational Health Pathology Respiratory System Safety Toxicology

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• Keywords:
  Analytical-models Carbon-compounds Cell-alteration Cell-transformation Cellular-reactions Chemical-deposition Chemical-properties Exposure-assessment Genetic-factors Inhalation-studies Laboratory-animals Laboratory-techniques Laboratory-testing Lung-cells Mass-spectrometry Metabolites Nanotechnology Physical-properties Physiological-chemistry Proteins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045963
• Citation:
  Toxicologist 2015 Mar; 144(1):268
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:66756a21e9628254bda2e91f9dacf1b2a4ad470aff603ce62d3d1c2e4c81b96f4aa00d0b8a813df84bf0feb5c465307b78f268322949eeaf5cb6c2c7ec7e46f8
• Download URL:
  https://stacks.cdc.gov/view/cdc/201169/cdc_201169_DS1.pdf
• File Type:
  [PDF - 218.10 KB ]