Biomonitoring of genotoxic effects for human exposure to nanomaterials: The challenge ahead

Our plain-English summary of Biomonitoring of genotoxic effects for human exposure to nanomaterials: The challenge ahead, by L. Gonzalez, M. Kirsch-Volders (Mutation Research. Reviews in Mutation Research, 2016).

The study

• Authors: L. Gonzalez, M. Kirsch-Volders
• Journal: Mutation Research. Reviews in Mutation Research
• Published: 2016;768:14-26
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposures to nanomaterials (NMs), with their specific physico-chemical characteristics, are likely to increase over the next years, as their production for industrial, consumer and medical applications is steadily rising. Therefore, there is an urgent need for the implementation of human biomonitoring studies of genotoxic effects after NM exposures in order to monitor and assure safety for workers and the general population. In this review, most commonly used biomarkers of early genetic effects were analyzed for their adequacy after NM exposures. A more in depth analysis of the ex vivo/in vitro lymphocyte MN assay was performed, although, in literature no studies are available using this assay for NM exposures. Therefore, the known factors determining the NMs tissue/cellular targets and the multiplicity of modes of action of NMs were summarized. The main pending questions are whether (1) lymphocytes are a NM target or an adequate surrogate tissue, (2) whether the buccal MN assay might be more suitable for NM exposures via inhalation or ingestion, as buccal cells might be exposed more directly. While the current state-of-the-art does not allow for drawing firm conclusions, major research gaps are identified and some cautious recommendations can be formulated. Therefore in vitro and in vivo studies should be conducted comparing methodologies side-by-side in the same subjects and for different types of NMs. The ex vivo/in vitro MN assay in its automated version, allowing objective analysis of large cohorts and detection of direct and indirect genotoxic effects, remains a valuable candidate for human biomonitoring to NM exposure. Considering the potential cancer risk from exposure to NMs and previous dramatic experiences with too late surveillance of occupational exposures to similar substances (e.g. to asbestos), there is an urgent need to define and implement adequate scientifically sound biomonitoring methods and programme for exposure to NMs.

Copyright © 2016 Elsevier B.V. All rights reserved.

In plain English

This review asked how to check people exposed to nanomaterials (materials where 50% or more of particles measure 1 to 100 nm in at least one dimension) for early genetic damage. Asbestos appeared only in passing: among known carcinogens nanomaterials have been compared with, and as a past case of too-late occupational surveillance. The authors reviewed laboratory and animal studies, including a PubMed search on where nanomaterials go in the body. They focused on the ex vivo/in vitro lymphocyte micronucleus (MN) assay, which examines blood cells from people exposed in the body. They found no studies using it for nanomaterials. They summarized the animal studies as showing that inhaled or swallowed nanomaterials may reach other organs via the bloodstream, but at low levels (under 1% of the dose). Citing lower uptake by lymphocytes than by some other cells, the authors concluded that firm conclusions were not yet possible and that lymphocytes might underestimate the risk from undissolved nanomaterials. They recommended comparing the buccal (cheek-cell) MN assay side by side with the lymphocyte assay, which they still called a valuable candidate.

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
• Who was studied: Published in vitro (cell) and in vivo (mainly rodent) studies of nanomaterials, including studies found by a PubMed search on nanomaterial biodistribution. The number of studies reviewed is not stated.
• Exposure: Nanomaterials, defined as materials in which 50% or more of the particles in the number size distribution have one or more external dimensions of 1 to 100 nm. Examples include titanium dioxide, silica, gold, silver and zinc oxide nanoparticles, and carbon nanotubes, given by inhalation or intra-tracheal instillation, by mouth, on the skin or by intravenous injection. Asbestos was not studied. The authors mentioned it among known carcinogens with which parallels have been drawn, and as a past example of too-late surveillance of occupational exposure.
• Main results:
  • The authors found no published studies that had used the ex vivo/in vitro lymphocyte MN assay (the biomonitoring version, on lymphocytes exposed in the body) for nanomaterial exposures.
  • The authors summarized the animal studies as showing that exposure by intra-tracheal instillation or inhalation and by ingestion may lead to nanomaterials moving to other organs through the bloodstream, although at low levels (less than 1% of the administered dose).
  • A cited laboratory study found that zinc oxide nanoparticles caused a 1.4-fold increase in micronuclei in lymphocytes, compared with a 4-5-fold increase in A549 lung carcinoma and U87 glioma cells. The authors took this as a sign of limited uptake by lymphocytes.
  • The authors concluded that using lymphocytes to follow exposure to undissolved nanomaterials may underestimate genotoxic risk.
  • Some rodent studies found micronuclei at the primary contact site (colon after oral silica nanoparticles; lung cells after inhaled multi-walled carbon nanotubes) but not in bone marrow. The authors said this showed that the choice of tissue tested matters.
  • In the authors' assessment, the lymphocyte MN assay can detect the known types of nanomaterial genotoxicity, is predictive of cancer risk, and has a validated automated system for large cohorts. In their view, the chromosomal aberration and comet assays do not have all three features.
• The authors' conclusion: The authors concluded that the automated ex vivo/in vitro MN assay remains a valuable candidate for human biomonitoring of nanomaterial exposure. They recommended comparing it side by side with the buccal MN assay in the same subjects. Citing past experience with too-late surveillance of occupational exposures such as asbestos, they called the need for biomonitoring methods and programmes urgent.
• Limitations the authors state:
  • The authors stated that the current state of knowledge does not allow firm conclusions.
  • The biodistribution studies used many different nanomaterials, animal models, detection methods and ways of expressing data.
  • The observations rest on a limited number of studies of a limited number of nanomaterials.
  • Doses used in the animal experiments were relatively high compared with real-life exposures.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Occupational Exposure.

Related studies

• Reprint of "Biomonitoring of genotoxic effects for human exposure to nanomaterials: The challenge ahead" — L. Gonzalez, M. Kirsch-Volders (2016)
• In vitro genotoxicity data of nanomaterials compared to carcinogenic potency of inorganic substances after inhalational exposure — M. Roller (2011)
• Cytotoxic and genotoxic effects of calcium silicates on human lymphocytes in vitro — M. Aslam, N. Fatima, et al. (1993)
• Validity of the Lymphocyte Cytokinesis-Block Micronucleus Assay (L-CBMN) as biomarker for human exposure to chemicals with different modes of action: A synthesis of systematic reviews — M. Kirsch-Volders, M. Fenech, et al. (2018)
• Genotoxic effects of asbestos in humans — M. Dusinská, A. Collins, et al. (2004)
• Genotoxic mechanisms of asbestos fibers: role of extranuclear targets — A. Xu, X. Huang, et al. (2007)

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