Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: a 1-year postexposure study

Details

• Personal Author:
  Andrew M ; Battelli L ; Castranova, Vincent ; Dong C ; Ducatman B ; Guo NL ; Porter DW ; Qian Y ; Raese R ; Snyder Talkington BN ; Wolfarth MG
• Description:
  Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 microg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-microg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 microg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms. [Description provided by NIOSH]
• Subjects:
  Asbestos Fibrosis Immune System Inorganic Chemicals Laboratories Lung Lung Diseases Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Alveolar Cells Cell Signaling Dose Response Exposure Assessment Gene Expression Gene Regulation Genomics Histopathology Immune Reaction Laboratory Animals Laboratory Testing Lung Fibrosis Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotubes Pulmonary Effects Pulmonary System Disorders

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• ISSN:
  1528-7394
• 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:
  352-366
• Volume:
  79
• Issue:
  8
• NIOSHTIC Number:
  nn:20047898
• Citation:
  J Toxicol Environ Health A 2016 Apr; 79(8):352-366
• Contact Point Address:
  Yong Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, USA
• Email:
  yaq2@cdc.gov
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d57e79ec244f09da15c7a32ba3bcaf50d4913f0249d3624a16ee64d49531e5dee37f888107e6eaca5a868eacf2977c3dbd76eaa0898fe3c6c296579ad0ded6ca
• Download URL:
  https://stacks.cdc.gov/view/cdc/202841/cdc_202841_DS1.pdf
• File Type:
  [PDF - 1.78 MB ]