Conventional and novel "omics"-based approaches to the study of carbon nanotubes pulmonary toxicity

Our plain-English summary of Conventional and novel "omics"-based approaches to the study of carbon nanotubes pulmonary toxicity, by C. Ventura, A. Sousa-Uva, J. Lavinha, et al (Environmental and Molecular Mutagenesis, 2018).

The study

• Authors: C. Ventura, A. Sousa-Uva, J. Lavinha, M.J. Silva
• Journal: Environmental and Molecular Mutagenesis
• Published: 2018;59(4):334-362
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The widespread application of carbon nanotubes (CNT) on industrial, biomedical, and consumer products can represent an emerging respiratory occupational hazard. Particularly, their similarity with the fiber-like shape of asbestos have raised a strong concern about their carcinogenic potential. Several in vitro and in vivo studies have been supporting this view by pointing to immunotoxic, cytotoxic and genotoxic effects of some CNT that may conduct to pulmonary inflammation, fibrosis, and bronchioloalveolar hyperplasia in rodents. Recently, high throughput molecular methodologies have been applied to obtain more insightful information on CNT toxicity, through the identification of the affected biological and molecular pathways. Toxicogenomic approaches are expected to identify unique gene expression profiles that, besides providing mechanistic information and guiding new research, have also the potential to be used as biomarkers for biomonitoring purposes. In this review, the potential of genomic data analysis is illustrated by gene network and gene ontology enrichment analysis of a set of 41 differentially expressed genes selected from a literature search focused on studies of C57BL/6 mice exposed to the multiwalled CNT Mitsui-7. The majority of the biological processes annotated in the network are regulatory processes and the molecular functions are related to receptor-binding signalling. Accordingly, the network-annotated pathways are cell receptor-induced pathways. A single enriched molecular function and one biological process were identified. The relevance of specific epigenomic effects triggered by CNT exposure, for example, alteration of the miRNA expression profile is also discussed in light of its use as biomarkers in occupational health studies. Environ. Mol. Mutagen. 59:334-362, 2018. © 2018 Wiley Periodicals, Inc.

© 2018 Wiley Periodicals, Inc.

In plain English

This article was a review of published laboratory and animal research on the lung effects of carbon nanotubes, a manufactured nanomaterial. It was not a study of asbestos or of people, and most findings it describes come from other studies. The authors also ran their own computer analysis of gene-activity data from four published studies of C57BL/6 mice exposed to one multiwalled carbon nanotube, Mitsui-7. No gene appeared in the available lists of changed genes from all four studies, and one study's list was incomplete. Two of them (Poulsen et al. 2013 and Snyder-Talkington et al. 2016a) shared 41 changed genes. Of these, four related to inflammation and none to fibrosis. The analysis of the 41 genes found helicase activity as the single enriched molecular function and response to interferon-gamma as the only enriched biological process. The pathways it identified included B cell receptor and Toll-like receptor signaling. The authors concluded the analysis could help reveal how Mitsui-7 affects the lungs. They also called the lack of reproducibility among the four studies worrying and said the findings need validation in workers with known exposure.

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: Review of in vitro, rodent, toxicogenomic and toxicoepigenomic studies of carbon nanotube lung toxicity, plus the authors' own gene network and gene ontology enrichment analysis of published gene-expression data
• Who was studied: For the authors' own analysis: published gene sets from four studies of C57BL/6 mice exposed to the multiwalled carbon nanotube Mitsui-7 (Pacurari et al. 2011, Guo et al. 2012, Poulsen et al. 2013, Snyder-Talkington et al. 2016a)
• Exposure: Carbon nanotubes (single-walled, double-walled and multiwalled) in the reviewed studies. The authors' own analysis used the multiwalled carbon nanotube Mitsui-7, given to mice by intratracheal instillation (Poulsen et al. 2013, analysed at 24 hr) or by pharyngeal aspiration (Snyder-Talkington et al. 2016a, analysed at one year).
• Main results:
  • In the available gene sets from the four Mitsui-7 mouse studies, no altered gene was common to all of them. The Guo et al. (2012) list was incomplete.
  • 41 differentially expressed genes were shared between the Poulsen et al. (2013) and Snyder-Talkington et al. (2016a) studies.
  • In those two studies, the same significant gene expression changes occurred at exposure doses differing by up to two orders of magnitude.
  • When the overlapping genes were filtered for inflammation and fibrosis, four inflammation-related genes remained (Ccl19, Ccl5, Cd14 and Myd88) and no fibrosis-related genes. The authors called the lack of fibrosis-related genes unexpected.
  • The functional interaction network consisted of 32 genes in four modules of highly interacting genes, plus 17 linker genes.
  • Gene ontology enrichment of the 41 genes found helicase activity as the single enriched molecular function (P value 1.27E-02) and response to interferon-gamma as the only enriched biological process (P value 4.55E-02).
  • The annotated pathways included cell receptor-induced pathways, such as B cell receptor signaling and Toll-like receptor signaling.
• The authors' conclusion: The authors concluded that their bioinformatics analysis of published transcriptomic data has the potential to reveal the molecular pathways of Mitsui-7 effects in the lungs and to point to future targets for studying how it acts.
• Limitations the authors state:
  • For the Guo et al. (2012) study, only 59 genes could be included because the full gene list was not available.
  • The four supposedly similar studies lacked reproducibility, and larger datasets are needed to validate the findings.
  • The differentially expressed genes have to be confirmed by independent studies.
  • Considered in isolation, the identified pathways may not distinguish Mitsui-7 exposure from exposure to other inhaled toxicants.
  • Occupational studies of carbon nanotube exposure were still missing, and the genomic findings need validation in workers with known exposure levels.
  • Lung structure and function differ significantly between rodents and humans.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Inflammation, Fibrosis, Biomarker.

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