Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses

Details

• Personal Author:
  Benkovic SA ; Bunker KL ; Cena LG ; Dinu CZ ; Dong C ; Hubbs, Ann F. ; Kashon ML ; Keane MJ ; Lowry DT ; Mastovich JT ; McCawley M ; Porter DW ; Reynolds SH ; Salisbury JL ; Sargent LM ; Siegrist KJ ; Sparrow MC ; Sturgeon JL ; Young S-H
• Description:
  Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 microg/cm2 MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 microm optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Chromosomes Cytotoxins DNA Irritants Laboratories Lung Lung Diseases Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Cell-alteration Cell-cultures Cell-damage Chromosome-damage Chromosome-disorders Cytotoxicity DNA-damage Dose-response Exposure-limits Gene-mutation Genotoxic-effects Humans Laboratory-testing Lung-cancer Mitosis Nanotechnology Particle-aerodynamics Permissible-concentration-limits Respiratory-irritants Therapeutic-agents Tumors

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• ISSN:
  1743-8977
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 3 ; OSHA Region 5 ; Pennsylvania ; 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:
  6
• Volume:
  11
• NIOSHTIC Number:
  nn:20043900
• Citation:
  Part Fibre Toxicol 2014 Jan; 11:6
• Contact Point Address:
  Cerasela Zoica Dinu, Department of Chemical Engineering, Benjamin M. Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV 26505, USA
• Email:
  cerasela-zoica.dinu@mail.wvu.edu
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  West Virginia University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Particle and Fibre Toxicology
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e69a746aaf2cbe2e6fb84c15acc49be984fc19aa696c7f24ea741ddf353246dd7cd44b16a42105267b24279c0ab507a5cc9a5a57537c7d0d8959fbfbf7bf59e5
• Download URL:
  https://stacks.cdc.gov/view/cdc/199772/cdc_199772_DS1.pdf
• File Type:
  [PDF - 2.66 MB ]