Mesothelioma: Identical Routes to Malignancy from Asbestos and Carbon Nanotubes

Our plain-English summary of Mesothelioma: Identical Routes to Malignancy from Asbestos and Carbon Nanotubes, by J. Port, D.J. Murphy (Current Biology, 2017).

The study

• Authors: J. Port, D.J. Murphy
• Journal: Current Biology
• Published: 2017;27(21):R1173-R1176
• Type of article: Comment
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure of laboratory mice to carbon nanotubes mimics exposure to asbestos, from initial and chronic inflammation, through loss of the same tumour-suppressor pathways and eventual sporadic development of malignant mesothelioma. Fibres of a similar nature may pose significant health risks to humans.

Copyright © 2017 Elsevier Ltd. All rights reserved.

In plain English

This article was a short commentary in Current Biology, not an original study. The authors described a mouse experiment by Chernova and colleagues, in the same issue, that injected long-fibre asbestos or long-fibre carbon nanotubes into the chest lining (pleura). As the commentary reported it, both caused similar chronic inflammation, similar changes in gene activity, and activation of the same signalling pathways. By 6 months, lesions in both groups showed increased cell growth and oxidative DNA damage. By 12 to 20 months, 10 to 25% of mice given carbon nanotubes (3 independent cohorts) and 9% given asbestos developed pleural mesothelioma, with the same latency. Tumours from both groups had reduced expression of the tumour-suppressor gene Cdkn2a. Pre-malignant lesions showed sporadic loss of these proteins and hypermethylation of the gene, which the authors said would suggest it was silenced before cancer developed. The authors concluded that carbon nanotubes with asbestos-like dimensions drive the same disease as long-fibre asbestos and present a comparable risk. They called for tighter regulation and further research in living animals.

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: Commentary (Current Biology 'Dispatch') on a mouse experiment by Chernova et al. published in the same issue; not original research
• Who was studied: Laboratory mice in the Chernova et al. study, including 3 independent cohorts exposed to carbon nanotubes; the commentary does not give the number of mice
• Exposure: Injection into the pleura of long-fibre asbestos (LFA, fibre type not named in the commentary) or long-fibre carbon nanotubes (CNT), compared with vehicle control and short-fibre forms of each
• Main results:
  • As reported by the commentary, at one and twelve weeks after injection both fibre types caused a similar degree of chronic inflammation
  • Tissue exposed to the long-fibre forms of asbestos or carbon nanotubes showed a similar pattern of altered gene expression, compared with vehicle control or short-fibre forms
  • Both fibre types activated the same signalling pathways seen in human mesothelioma (SRC, FAK, ERK, AKT/mTORC1, STAT)
  • By 6 months, lesions in both the asbestos and carbon nanotube groups showed increased cell proliferation and oxidative DNA damage
  • By 12 to 20 months, 10 to 25% of mice exposed to carbon nanotubes (3 independent cohorts) and 9% of mice exposed to asbestos developed pleural mesothelioma; latency was the same for both
  • Tumours from both fibre types had reduced expression of p19Arf and p16Ink4a (products of Cdkn2a); tumours from carbon nanotubes also showed allelic loss of p19Arf
  • Pre-malignant inflammatory lesions showed sporadic loss of p19Arf and p16Ink4a expression without allelic loss
  • Pre-malignant lesions in mice exposed to either fibre showed hypermethylation at the Cdkn2a locus; the authors said these data would suggest epigenetic silencing occurs before progression to malignancy
  • Tumours from either fibre showed no loss of NF2 protein expression
• The authors' conclusion: The authors concluded that carbon nanotubes with asbestos-like dimensions drive the same disease as long-fibre asbestos and present a comparable risk. They saw the study as an opportunity for tighter regulation of carbon nanotube production, use and disposal.
• Limitations the authors state:
  • The authors said further in vivo investigation is needed of how disease develops from the pre-malignant state to clinical mesothelioma

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chronic Inflammation, Malignant Mesothelioma.

Related studies

• Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura — F.A. Murphy, C.A. Poland, et al. (2011)
• Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung — D. Crouzier, S. Follot, et al. (2010)
• Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model — D.K. Lee, S. Jeon, et al. (2018)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice — A. Yamaguchi, T. Fujitani, et al. (2012)
• Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes — Y.J. Arnoldussen, V. Skaug, et al. (2018)

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