Systematic analysis of multi-walled carbon nanotube-induced cellular signaling and gene expression in human small airway epithelial cells

Details

• Personal Author:
  Castranova, Vincent ; Dong C ; Guo NL ; Leonard, Stephen S. ; Pacurari M ; Qian Y ; Schwegler-Berry D ; Snyder-Talkington BN
• Description:
  Multi-walled carbon nanotubes (MWCNT) are one of the most commonly produced nanomaterials, and pulmonary exposure during production, use, and disposal is a concern for the developing nanotechnology field. The airway epithelium is the first line of defense against inhaled particles. In a mouse model, MWCNT were reported to reach the alveolar space of the lung after in vivo exposure, penetrate the epithelial lining, and result in inflammation and progressive fibrosis. This study sought to determine the cellular and gene expression changes in small airway epithelial cells (SAEC) after in vitro exposure to MWCNT in an effort to elucidate potential toxicity mechanisms and signaling pathways. A direct interaction between SAEC and MWCNT was confirmed by both internalization of MWCNT as well as an interaction at the cell periphery. Following exposure, SAEC showed time-dependent increases in reactive oxygen species production, total protein phospho-tyrosine and phospho-threonine levels, and migratory behavior. Analysis of gene and protein expression suggested altered regulation of multiple biomarkers of lung damage, carcinogenesis, and tumor progression, as well as genes involved in related signaling pathways. These results demonstrate that MWCNT exposure resulted in the activation of SAEC. Gene expression data derived from MWCNT exposure provides information that may be used to elucidate the underlying mode of action of MWCNT in the small airway and suggest potential prognostic gene signatures for risk assessment. Erratum: Toxicol Sci 2013 Aug; 134(2):427. The corresponding author information was incorrect. Correspondence should be sent to Nancy L. Guo (fax: 304-293-4667; email: lguo@hsc.wvu.edu) or Yong Qian (fax: 304-285-5838; email: yaq2@cdc.gov). The publisher regrets the error. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Carcinogens Fibrosis Genetics Inhalation Exposure Irritants Laboratories Lung Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Airway Epithelial Damage Author Keywords: Multi-walled Carbon Nanotubes Carcinogenesis Cellular-reactions Exposure-levels Genes Inhalants Laboratory-animals Molecular Mechanisms Nanotechnology Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-irritants Respiratory-system-disorders Risk-factors Signaling Pathways Tumors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  79-89
• Volume:
  133
• Issue:
  1
• NIOSHTIC Number:
  nn:20042182
• Citation:
  Toxicol Sci 2013 May; 133(1):79-89
• Contact Point Address:
  Nancy L. Guo, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300
• Email:
  lguo@hsc.wvu.edu
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ef5fa0c9938268546ae1cc53a4f8d3e2444a499c621a75a4e1446e28a15651ffccda9827dc80c798643e12ece27d74d6bc3ca44c61c918546b57e57ae590fc12
• Download URL:
  https://stacks.cdc.gov/view/cdc/194484/cdc_194484_DS1.pdf
• File Type:
  [PDF - 815.57 KB ]