Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

Our plain-English summary of Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons, by A.A. Shvedova, N. Yanamala, E.R. Kisin, et al (American Journal of Physiology. Lung Cellular and Molecular Physiology, 2014).

The study

• Authors: A.A. Shvedova, N. Yanamala, E.R. Kisin, A.V. Tkach, A.R. Murray, A. Hubbs, M.M. Chirila, P. Keohavong, L.P. Sycheva, V.E. Kagan, V. Castranova
• Journal: American Journal of Physiology. Lung Cellular and Molecular Physiology
• Published: 2014;306(2):L170-82
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

In plain English

This animal experiment exposed female C57BL/6 mice by a single pharyngeal aspiration of SWCNT (40 micrograms), carbon nanofibers (CNF, 40 or 120 micrograms), UICC crocidolite asbestos (120 micrograms) or saline, or by inhalation of SWCNT (5 mg/m3, 5 h/day, 4 days; lung burden 5 micrograms). Mice were killed 1 year later; separate subsets provided lavage, histopathology and lung homogenates, and micronuclei and nuclear protrusions were reported for SWCNT inhalation mice. CNF and asbestos (120 micrograms) raised all lavage cellular markers of inflammation and IL-12p70 (230% and 285% of control); SWCNT aspiration raised no lavage cell count significantly, though granulomatous bronchointerstitial pneumonia was seen histologically, and SWCNT inhalation gave a 21.7-fold of control neutrophil rise. Lung collagen rose after aspiration of SWCNT (40 micrograms), CNF (120 micrograms) and asbestos (120 micrograms), and was 250% of control after SWCNT inhalation versus 166% after SWCNT aspiration. K-ras mutations increased after SWCNT and CNF (120 micrograms) but none were detected after asbestos. The authors concluded SWCNT were the most fibrogenic of the three particles; no tumors were detected.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (mouse inhalation and pharyngeal aspiration study with assessment 1 year postexposure)
• Who was studied: Specific pathogen-free adult female C57BL/6 mice (8-10 weeks old), 6 mice per group per endpoint, studied at a NIOSH animal facility, killed 1 year after exposure
• Exposure: Pharyngeal aspiration of SWCNT (40 micrograms/mouse), CNF (40 and 120 micrograms/mouse) or UICC crocidolite asbestos (120 micrograms/mouse), with saline vehicle controls; a further group was exposed by inhalation to SWCNT (5 mg/m3, 5 h/day for 4 days, lung burden 5 micrograms) with filtered-air controls
• Main results:
  • Additional mice were exposed by inhalation to SWCNT at 5 mg/m3, 5 h/day for 4 days, giving a lung burden of 5 micrograms
  • One year after aspiration, SWCNT (40 micrograms) caused no significant cellular inflammation in lavage, whereas SWCNT inhalation (5 micrograms lung burden) gave a 21.7-fold of control rise in neutrophils with raised macrophages and lymphocytes
  • Aspiration of CNF or asbestos at the higher mass lung burden (120 micrograms) produced greater elevation of all cellular inflammation markers than the lower-burden groups
  • Lavage LDH remained significantly raised 1 year after CNF aspiration (147% of control at 40 micrograms; 192% at 120 micrograms)
  • Total BAL protein was significantly elevated after CNF 120 micrograms (196% of control); neither SWCNT nor asbestos raised BAL protein concentrations
  • IL-12p70 in lavage fluid was elevated 1 year after aspiration of CNF or asbestos at 120 micrograms (230% and 285% of control respectively); SWCNT by either route produced no cytokine change
  • Lung collagen was raised above control in the aspiration groups shown (SWCNT 40 micrograms, CNF 120 micrograms, asbestos 120 micrograms); after SWCNT inhalation (5 micrograms lung burden) it was 250% of control versus 166% of control after aspiration of 40 micrograms SWCNT
  • By collagen levels, SWCNT were the most fibrogenic particle at 1 year, followed by CNF and asbestos
  • Granulomatous bronchointerstitial pneumonia was seen 1 year after aspiration of SWCNT (40 micrograms), asbestos (120 micrograms) and CNF (40 and 120 micrograms)
  • Mice given asbestos aspiration also showed pleuritis, mesothelial cell hyperplasia and/or atypia and vasculitis
  • Granulomatous lymphadenitis occurred in the tracheobronchial lymph nodes with all particles; asbestos fibres were generally cell associated and sometimes caused giant cell formation, while CNF were not associated with giant cells
  • K-ras mutation incidence rose 1 year after SWCNT (33% over controls by inhalation, 20% by aspiration) and after CNF at 120 micrograms (50% over control), while no mutations were detected after asbestos aspiration at 120 micrograms
  • Micronuclei and micronuclei plus nuclear protrusions in lung cells were significantly increased 1 year after SWCNT inhalation (5 micrograms lung burden)
  • Raman microscopy indicated 5 to 10% of the initial 40 microgram SWCNT lung burden was still present in the lungs 1 year after exposure
  • No tumors were detected in this 1-year study
• The authors' conclusion: The authors concluded that at 1 year postexposure SWCNT were more fibrogenic than CNF or asbestos, and that long-term pulmonary toxicity of these materials depends not only on chemical composition but also on specific surface area and type of exposure
• Limitations the authors state:
  • The authors stated that further studies in C57BL/6 and more susceptible mouse strains are needed to clarify the possible carcinogenic potential of SWCNT and CNF
  • Histopathology was read unmasked, because the particles are visible in tissue sections so masked evaluation was not possible
  • Different subsets of animals were used for each endpoint, so lavage, histopathology and lung homogenate measurements came from different mice

Topics

Medical terms in this study, explained in our Lexicon: Fibrogenic, Pulmonary Fibrosis, Inflammation, Micronuclei, Asbestos Exposure.

Related studies

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• Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs — P. Kinaret, M. Ilves, et al. (2017)
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