Pulmonary Toxicity and Gene Expression Changes in Response to Multi-Walled Carbon Nanotube Exposure in Rats

Details

• Personal Author:
  Chen TB ; Joseph P ; McKinney W ; Orandle M ; Roberts, Jennifer R. ; Sager T ; Umbright C
• Description:
  Carbon-based nanomaterials have significant commercial and industrial applications and, therefore, human exposure to them potentially resulting in adverse health effects should be anticipated. Understanding the molecular mechanisms underlying the toxicity induced by carbon nanotubes has merit in the prevention of the adverse health effects potentially resulting from their exposures. Currently, a rat toxicity model was employed to investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to multi-walled carbon nanotubes (MWCNT). Rats were exposed, by whole-body inhalation exposure, to air or an aerosol containing MWCNT particles (5 mg/m3, 6 hours/day, 3 days). Toxicity and global gene expression profiles were determined in the lungs of the rats, 16-hours following the last exposure. MWCNT particles, often associated with alveolar macrophages (AMs), were detected in the lungs of the exposed rats. Lung histological changes resulting from MWCNT exposure were mild and consisted mainly of interstitial accumulation of macrophages. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and PMNs, oxidant production by phagocytes, and levels of multiple cytokines (IL-1beta, IL-10, MCP-1, MIP-2, and TNF-alpha) were significantly altered in response to inhalation exposure to MWCNT in the rats. Global gene expression profiling by next generation sequencing identified a large number of significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in the lungs of the MWCNT exposed rats, compared with the controls. Bioinformatics analysis of the gene expression data identified significant enrichment of several diseases/biological functions (for example, cancer, organismal injury and abnormalities, cell cycle, respiratory disease, cellular movement, and inflammatory response) and canonical pathways (for example, LXR/RXR activation, granulocyte and agranulocyte adhesion and diapedesis, complement system, acute phase response, and atherosclerosis signaling). Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT. [Description provided by NIOSH]
• Subjects:
  Aerosols Blood Cells, Cultured Environmental Exposure Genetics Immune System Laboratories Lung Macrophages Microbiology Occupational Health Oxidants Respiratory System Safety Toxicology

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• Keywords:
  Alveolar Cells Analytical Models Bioinformatics Biological Function Carbon Nanotubes Cell Alteration Cell Cultures Cell Signaling Cytokines Diseases Dose Response Exposure Assessment Exposure Levels Gene Expression Genes Histopathology Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Cells Lung Function Microscopic Analysis Molecular Structure Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Oxidative Processes Phagocytes Phagocytic Activity Proteins Pulmonary Effects Pulmonary Function Tissue Culture Toxic Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; 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:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051264
• Citation:
  Toxicologist 2018 Mar; 162(1):420
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:76699db784a9d17ba345188a8f61642fc09d2e0511a813e4f3715b6ee14edf8b5e32a7eabd234350e2b3a9fe4e9a7504519dfe2a8090132d4148bc0808ee8326
• Download URL:
  https://stacks.cdc.gov/view/cdc/211321/cdc_211321_DS1.pdf
• File Type:
  [PDF - 832.64 KB ]