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

Our plain-English summary of Reprint 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;770(Pt A):204-216
• Type of article: Review
• Cited by: 4 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 is a review, not a new study, of research on nanomaterials (particles mostly 1 to 100 nanometres), not asbestos. The authors weighed mostly laboratory and animal research to judge which tests could monitor genetic damage in exposed people. They focused on the ex vivo/in vitro lymphocyte micronucleus assay, which examines white blood cells taken from exposed people; they said it detects both direct and indirect genetic damage. They found no published studies using this version for nanomaterial exposures, though laboratory studies had exposed lymphocytes to nanomaterials in culture. In their overall reading of animal studies, inhaled or swallowed nanomaterials reached other organs through the blood only at low levels, below 1% of the dose, and results varied. Because lymphocytes appeared to take up nanomaterials poorly, the authors wrote that the test might underestimate risk from undissolved nanomaterials. They proposed comparing it side by side with a cheek-cell (buccal) micronucleus test. The authors stated that firm conclusions were not yet possible. Citing asbestos, where surveillance of exposed workers came too late, they concluded that sound biomonitoring for nanomaterials is urgently needed.

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 in vitro, animal and human studies on nanomaterials and biomarkers of genetic effects
• Who was studied: No people were studied directly. The authors reviewed published laboratory (cell) and rodent studies, plus a few human studies, on how nanomaterials spread in the body, are taken up by cells and damage genetic material. Biodistribution studies were found through a PubMed search. The number of studies and the search dates are not given.
• Exposure: Nanomaterials such as gold, titanium dioxide, silica and iron oxide nanoparticles and carbon nanotubes, given by inhalation or intra-tracheal instillation, by mouth, on the skin or by intravenous injection. Asbestos fibers are mentioned only as a comparison with known carcinogens.
• Main results:
  • The authors found no published studies that used the ex vivo/in vitro lymphocyte micronucleus assay for nanomaterial exposures. In this assay, T lymphocytes exposed in the body are cultured and then examined. It differs from the in vitro micronucleus assay, in which lymphocytes are exposed during culture; the authors did discuss laboratory studies of that kind.
  • The article describes the two versions of the assay: the ex vivo/in vitro assay looks at lymphocytes exposed in the body, and the in vitro assay looks at lymphocytes exposed during culture.
  • In the authors' overall reading of the animal studies, exposure by intra-tracheal instillation or inhalation and by ingestion could lead to nanomaterials moving to other organs through the bloodstream, but at low levels. They put these levels at less than 1% of the administered dose.
  • Individual results varied. In one reviewed rat study, after intra-tracheal instillation the smallest (1.4 nm) gold nanoparticles were found in skin (1.5%), kidneys (1.2%), urine (1.1%), liver (0.7%) and blood (0.6%).
  • One reviewed in vitro study (Tavares et al.) reported that lymphocytes have a limited capacity to take up nanomaterials. Zinc oxide nanoparticles produced a 1.4-fold increase in micronuclei in lymphocytes, compared with a 4-5-fold increase in A549 lung carcinoma cells and U87 glioma cells.
  • The authors wrote that using lymphocytes to follow up exposure to undissolved nanomaterials may underestimate genotoxic risk. They also wrote that uptake is potentially not an issue for soluble nanomaterials or those causing systemic effects.
  • No data existed on how well human buccal (cheek) and nasal cells take up nanomaterials, and data for human lymphocytes were scarce.
  • Of eight positive in vivo rodent genotoxicity studies the authors listed, five observed genotoxic effects in secondary tissues.
  • The authors judged that the lymphocyte micronucleus assay can detect both direct and indirect genotoxic effects, has been shown to predict cancer risk, and has a validated automated system for large cohorts. They wrote that the chromosomal aberration and comet assays do not have all three of these features.
• The authors' conclusion: The authors concluded that, given the potential cancer risk from nanomaterials and past experience with occupational asbestos exposures where surveillance came too late, sound biomonitoring methods and programmes for nanomaterial exposure are urgently needed. In their view the automated lymphocyte micronucleus assay remains a valuable candidate, and it should be compared with the buccal micronucleus assay in the same subjects.
• Limitations the authors state:
  • The authors stated that the current state of knowledge does not allow firm conclusions.
  • The observations rest on a limited number of studies of a limited number of nanomaterials.
  • The biodistribution studies were hard to compare because they used different nanomaterials, animal models, detection methods and ways of expressing data.
  • Doses used in the animal experiments were relatively high compared with real-life exposures, so a similar fraction of a real-life exposure might go undetected in a human biomonitoring study.

Topics

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

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