Genotoxicity of pristine, heat-treated, and nitrogen-doped multi-walled carbon nanotubes at occupationally relevant doses

Details

• Personal Author:
  Bunker K ; Cena L ; Endo M ; Kashon M ; Lowry D ; Mastovich J ; McCawley M ; Mercer R ; Porter, Dale ; Reynolds S ; Salisbury J ; Sargent L ; Siegrist K ; Sparrow M ; Terrones M ; Tsuruoka S ; Bunker K ; Cena L ; Endo M ; Kashon M ; Lowry D ; Mastovich J ; McCawley M ; Mercer R ; Porter, Dale ; Reynolds S ; Salisbury J ; Sargent L ; Siegrist K ; Sparrow M ; Terrones M ; Tsuruoka S
• Description:
  The unique physiochemical properties of multi-walled carbon nanotubes (MW) make respiratory exposures likely in workers. Previously, in vitro exposure to MW has led to cell cycle disruption, chromosome errors, mitotic aberrations, and increased clonal growth at occupationally relevant doses. Combining the effects seen in vitro with the potential for lung deposition in the workplace, MW should be considered as a potential health hazard. Altering the physiochemical properties of MW has been shown to reduce toxicity. Nitrogen-doped MWCNT (NDMW) material is less inflammatory than pristine MW (PMW). PMW exposed to extremely high temperatures (HTMW) removes impurities and reduces their bioreactivity in acellular systems. To investigate genotoxicity of NDMW and HTMW compared to PMW at an occupationally relevant dose, we used two cell types, an immortalized human lung epithelial cell BEAS-2B and primary lung epithelial cell SAEC. All MW were necrotic in both cell types at the 24 microg/cm2 dose. There was no effect on the cell cycle in BEAS-2B cells. All MW induced a significant G0/G1 phase block in SAEC cells after 24 hour exposure to 24 microg/cm2 and a significant G1/S phase block after 72 hour exposure to 2.4 microg/cm2. Clonal growth in SAEC cells was inhibited by PMW at all doses, HTMW at 24 microg/cm2 and NDMW at 2.4 and 24 microg/cm2. By contrast, number and size of colonies was increased by 0.024 and 0.24 microg/cm2 HTMW and NDMW and 2.4 microg/ cm2 HTMW. Significant increases in mitotic aberrations, predominantly monopolar, were observed by exposure to all MW for 24 hours. All MW were found to penetrate the nucleus and associate with the DNA, mitotic spindle and centrosomes. Nuclear penetrations were greatest for the PMW followed by HTMW and NDMW, respectively. Significantly increased fragmentation of the centrosome and centromere were found in response to all MW exposure at all doses indicating a possible mechanism of genotoxicity, however a lower limit was not apparent. A dose-dependent increase in aneuploidy was observed from exposure to all MWs. These data indicate that altering the physiochemical properties of MWs may not reduce their genotoxic effect. [Description provided by NIOSH]
• Subjects:
  Lung Occupational Health Respiratory System Safety Toxicology
• Keywords:
  DNA Damage Genotoxic Effects Genotoxicity Lung Cells Multi-walled Carbon Nanotubes MWCNT Nanotoxicology
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  Louisiana ; Minnesota ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 6 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  416-417
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047704
• Citation:
  Toxicologist 2016 Mar; 150(1):416-417
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:998c60dbd74cc671aef7b6be8969ef2a432d1dca879d9add3f41f13da45ec7a958ee9769f3bb66b68e917268dad5eb6bd2834a310d0175ba92b00c8f6f09367a
• Download URL:
  https://stacks.cdc.gov/view/cdc/202707/cdc_202707_DS1.pdf
• File Type:
  [PDF - 452.51 KB ]