Integration of inflammation, fibrosis, and cancer induced by carbon nanotubes

Our plain-English summary of Integration of inflammation, fibrosis, and cancer induced by carbon nanotubes, by J. Dong, Q. Ma (Nanotoxicology, 2019).

The study

• Authors: J. Dong, Q. Ma
• Journal: Nanotoxicology
• Published: 2019;13(9):1244-1274
• Type of article: Review
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Carbon nanotubes (CNTs) are nanomaterials with unique physicochemical properties that are targets of great interest for industrial and commercial applications. Notwithstanding, some characteristics of CNTs are associated with adverse outcomes from exposure to pathogenic particulates, raising concerns over health risks in exposed workers and consumers. Indeed, certain forms of CNTs induce a range of harmful effects in laboratory animals, among which inflammation, fibrosis, and cancer are consistently observed for some CNTs. Inflammation, fibrosis, and malignancy are complex pathological processes that, in summation, underlie a major portion of human disease. Moreover, the functional interrelationship among them in disease pathogenesis has been increasingly recognized. The CNT-induced adverse effects resemble certain human disease conditions, such as pneumoconiosis, idiopathic pulmonary fibrosis (IPF), and mesothelioma, to some extent. Progress has been made in understanding CNT-induced pathologic conditions in recent years, demonstrating a close interconnection among inflammation, fibrosis, and cancer. Mechanistically, a number of mediators, signaling pathways, and cellular processes are identified as major mechanisms that underlie the interplay among inflammation, fibrosis, and malignancy, and serve as pathogenic bases for these disease conditions in CNT-exposed animals. These studies indicate that CNT-induced pathological effects, in particular, inflammation, fibrosis, and cancer, are mechanistically, and in some cases, causatively, interrelated. These findings generate new insights into CNT adverse effects and pathogenesis and provide new targets for exposure monitoring and drug development against inflammation, fibrosis, and cancer caused by inhaled nanomaterials.

In plain English

This was a review article by two authors at the National Institute for Occupational Safety and Health on how inflammation, fibrosis and cancer caused by carbon nanotubes (CNTs) are connected. The authors summarized published laboratory studies, mainly in mice and rats exposed to single-walled and multi-walled CNTs (including Mitsui MWNT-7 and MWCNT-N) by inhalation, instillation, aspiration, or injection into the pleural, peritoneal or scrotal cavities, together with cell-culture work and a limited amount of human data on asbestos and on CNT workers. They reported that some CNTs resemble asbestos in high aspect ratio, low solubility and biopersistence, and that long fibers retained at the parietal pleura support a fiber length-pathogenicity relationship analogous to the asbestos "fiber pathogenicity paradigm". They noted that IARC classified MWNT-7 as possibly carcinogenic to humans (Group 2B), and other CNTs as Group 3. The authors concluded that accumulating evidence supports interconnected mechanisms behind CNT-induced inflammation, fibrosis and tumorigenesis, while noting that direct evidence linking fibrosis to cancer in CNT pathology is currently lacking.

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: narrative review of published laboratory (mainly rodent) and some human studies
• Who was studied: Published studies, mostly in mice and rats (tabulated rodent lung and mesothelial studies), plus cultured human and rodent cells and some human epidemiological/pathology data on asbestos and CNT workers
• Exposure: Carbon nanotubes: single-walled (SWCNT) and multi-walled (MWCNT) types, including Mitsui MWNT-7 and MWCNT-N, of varying length, diameter and rigidity, given by inhalation, intratracheal instillation, oropharyngeal aspiration, transtracheal intrapulmonary spraying, and intrapleural, intraperitoneal or intrascrotal injection; compared with asbestos and silica
• Main results:
  • The review reported that long CNTs retained at the parietal pleura cause persistent lesions, supporting a fiber length-pathogenicity relationship like that described for asbestos
  • The authors cited the IARC classification of MWNT-7 as Group 2B and of SWCNTs and other MWCNTs as Group 3
  • In a reviewed rat study (Suzui et al. 2016), MWCNT-N fractions given by transtracheal intrapulmonary spraying produced lung tumors in 14 of 38 exposed rats and none in untreated or vehicle controls
  • In a reviewed mouse study (Chernova et al. 2017), long MWCNTs (85% of fibers longer than 15 micrometres) instilled into the pleural cavity caused pleural mesotheliomas with carcinogenic potential similar to long asbestos
  • In a reviewed rat study (Nagai et al. 2011), MWNT-7 produced malignant mesotheliomas on the liver surface whereas tangled MWCNTs did not
  • The review cited human asbestos pathology data (Churg and Vedal 1994) on co-existence of pleural plaque and mesothelioma
  • The authors stated there is no available evidence of CNT-induced organ fibrosis in humans, only increased fibrotic mediators and biomarkers in body fluids of CNT workers
• The authors' conclusion: The authors concluded that inflammation, fibrosis and cancer induced by CNTs are mechanistically interconnected, and that this evidence base may inform risk assessment and the search for intervention targets
• Limitations the authors state:
  • Direct evidence linking fibrosis and cancer in CNT pathology is lacking, partly for want of suitable methods and models
  • Human studies of nanomaterial exposure and health effects are currently lacking, so human effects remain largely undefined
  • Comparing animal with human studies is difficult because of heterogeneous human disease, limited epidemiological data, exposure uncertainty, long latency and confounding
  • The authors state that research on these interactions in CNT pathology is at an early stage with major unresolved questions

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Fibrosis, Pneumoconiosis, Idiopathic, Pulmonary Fibrosis, 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)
• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)
• A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice — E.J. Park, J. Roh, et al. (2011)
• Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study — J.M. Dymacek, B.N. Snyder-Talkington, et al. (2018)
• 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)

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