Multiwalled carbon nanotube-induced lung tumors

Details

• Personal Author:
  Andrew M ; Battelli LA ; Castranova, Vincent ; Chen BT ; Endo M ; Frazer D ; Hubbs, Ann F. ; Kashon ML ; Lowry DT ; McKinney W ; Porter DW ; Reynolds SH ; Sargent L ; Siegrist K ; Staska L ; Tsuruoka S ; Andrew M ; Battelli LA ; Castranova, Vincent ; Chen BT ; Endo M ; Frazer D ; Hubbs, Ann F. ; Kashon ML ; Lowry DT ; McKinney W ; Porter DW ; Reynolds SH ; Sargent L ; Siegrist K ; Staska L ; Tsuruoka S
• Description:
  Carbon nanotubes have many promising applications. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, there is limited data on carcinogenicity of inhaled multi-walled carbon nanotubes (MWCNTs). We have therefore utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNTs act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single dose of either methylcholanthrene (MC, 10 microg/g BW, i.p.) or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNTs (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. The B6C3F1 mouse used in this study has intermediate susceptibility to lung carcinogenesis, and data obtained will have relevancy to existing human lung tumor data because lung tumors in this mouse strain exhibit many molecular and morphological similarities to human pulmonary tumors. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation. Twenty percent of the filtered air controls, 33% of the MWCNT-exposed, and 50% of the MC followed by air-exposure, had a mean of one tumor per mouse. By contrast, 100% of the mice which received MC followed by MWCNTs had tumors with an average of 3.6 tumors per mouse. Additionally, mice exposed to MWCNTs or MC followed by MWCNTs had larger tumor volumes than their corresponding air-exposed control groups. Our preliminary data suggests that MWCNT exposure promotes the growth of spontaneously and chemically initiated lung cells, resulting in the development of lung tumors. In this study, mouse MWCNT lung burden approximates feasible human occupational exposures. Therefore, the results of this ongoing study indicate that caution should be used to limit human exposures to MWCNTs. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cytotoxins DNA Environmental Monitoring Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Cell-alteration Cell-growth Cellular-reactions Cytotoxicity DNA-damage Dose-response Exposure-assessment Exposure-levels Inhalation-studies Laboratory-animals Laboratory-techniques Lung-burden Lung-cancer Lung-cells Lung-disease Lung-disorders Methyl-compounds Nanotechnology Pulmonary-disorders Pulmonary-system Tumors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 6 ; Texas ; 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:
  98
• Volume:
  132
• Issue:
  1
• NIOSHTIC Number:
  nn:20042400
• Citation:
  Toxicologist 2013 Mar; 132(1):98
• CAS Registry Number:
  3-Methylcholanthrene (CAS RN 56-49-5) ; Carbon (CAS RN 7440-44-0) ; 3-Methylcholanthrene (CAS RN 56-49-5) ; Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9a8c64c9d9df28887e51ce1a92060b66a8feaae2f1a756d3c8bfcf4f7e76093a34c95240b044cb3b03e8a8e38c0de6eee6e7c554c1164815d51f5efa5d31c8d4
• Download URL:
  https://stacks.cdc.gov/view/cdc/194632/cdc_194632_DS1.pdf
• File Type:
  [PDF - 582.56 KB ]