Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials

Our plain-English summary of Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials, by H. Nagai, S. Toyokuni (Archives of Biochemistry and Biophysics, 2010).

The study

• Authors: H. Nagai, S. Toyokuni
• Journal: Archives of Biochemistry and Biophysics
• Published: 2010;502(1):1-7
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Nano-sized durable fibrous materials such as carbon nanotubes have raised safety concerns similar to those raised by asbestos. However, the mechanism by which particulates with ultrafine structure cause inflammation and ultimately cancer (e.g. malignant mesothelioma and lung cancer) is largely unknown. This is partially because the particulates are not uniform and they vary in a plethora of factors. Such variances include length, diameter, surface area, density, shape, contaminant metals (including iron) and crystallinity. Each of these factors is involved in particulate toxicity both in vitro and in vivo. Thus, the elicited biological responses are incredibly complicated. Various kinds of fibers were evaluated with different cells, animals and methods. The aim of this review is to concisely summarize previous reports from the standpoint that activation of macrophages and mesothelial injury are the two major mechanisms of inflammation and possibly cancer. Importantly, these two mechanisms appear to be interacting with each other. However, there is a lack of data on the interplay of macrophage and mesothelium especially in vivo. Since fibrous nanomaterials present potential applications in various fields, it is necessary to develop standard evaluation methods to minimize risks for human health.

Copyright 2010 Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new study. The authors summarized earlier research on how long, durable fibers, namely asbestos and multi-walled carbon nanotubes (MWCNTs), may cause inflammation and cancer, including malignant mesothelioma. They organized the evidence around two proposed mechanisms that they suggested interact: persistent activation of macrophages (immune cells) and direct injury to epithelial and mesothelial cells. Their tables listed published animal and cell studies of MWCNTs. One listed study reported mesothelioma in 14 of 16 p53 hetero-knockout mice injected with MWCNTs, against 14 of 18 given crocidolite. Another reported mesothelioma in 6 of 7 rats after intrascrotal injection, against 0 of 10 given crocidolite. The authors described the data on macrophage activation as inconsistent. They found MWCNT toxicity to epithelial and mesothelial cells variable and contradictory. They attributed the differences between studies partly to fiber properties and methods, and they cautioned against applying rodent results directly to humans. The authors concluded that the fiber features driving these effects had yet to be determined.

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 previously published laboratory (cell) and animal studies
• Who was studied: Published studies, not people: in vivo animal studies of MWCNTs in rats and mice (Table 1), in vitro studies of MWCNTs on macrophages (Table 2), and in vitro studies on epithelial/mesothelial cells (Table 3)
• Exposure: Asbestos (background discussion of crocidolite, amosite, tremolite, anthophyllite, actinolite and chrysotile) and multi-walled carbon nanotubes; the authors used the term MWCNTs to cover both multi-walled carbon nanotubes and multi-walled carbon nanofibers
• Main results:
  • Among the in vivo studies the authors tabulated, the degree and nature of inflammation caused by MWCNTs differed between studies. The authors attributed this probably to differences in MWCNT properties, administration method, animal species and sex, and experimental design.
  • One study listed in Table 1 (intraperitoneal injection, p53 hetero-knockout C57BL/6 male mice) reported mesothelioma in 14/16 MWCNT-treated mice, compared with 14/18 in the positive control crocidolite group
  • Another study listed in Table 1 (intrascrotal injection, F344 male rats) reported mesothelioma in the peritoneal cavity in 6/7 MWCNT-treated rats, compared with 0/10 in the positive control crocidolite group
  • According to the earlier studies the authors reviewed, long fibers are more potent macrophage activators because macrophages cannot fully engulf them (described as 'frustrated phagocytosis')
  • The authors judged the data on the ability of MWCNTs to cause inflammation through macrophages to be inconsistent
  • The authors concluded that MWCNTs showed variable toxicity to epithelial/mesothelial cells, with contradictory observations on cytotoxicity, genotoxicity and entry into cells
• The authors' conclusion: The authors concluded that investigators had yet to identify the main fiber features that cause continuous macrophage activation and/or epithelial/mesothelial cell damage. They said this knowledge is needed to set global standards for assessing the risk of nano-sized fibrous materials, and that cell and animal studies would be needed for each kind of MWCNT until suitable surrogate markers are found.
• Limitations the authors state:
  • Reports of MWCNT toxicity to cell types other than epithelial/mesothelial cells, such as fibroblasts, were not included in the review
  • The authors noted differences between the respiratory systems of rodents and humans and cautioned against applying rodent data directly to humans
  • Results from injecting fibers into body cavities do not necessarily match those from inhalation

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Carcinogenesis, Malignant Mesothelioma, Lung Cancer, Macrophage, Mesothelium.

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