Towards a New Paradigm in Nano‐Genotoxicology: Facing Complexity of Nanomaterials’ Cellular Interactions and Effects

Gonzalez, Laetitia; Cundari, Enrico; Leyns, Luc; Kirsch‐Volders, Micheline

doi:10.1111/bcpt.12698

Cited by 11 publications

(4 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the different health effects that NMs can cause, those related to their potential interaction with DNA requires special attention. Thus, the detection of the genotoxic effects induced by NMs is emerging as a specific research field covering such demands [2,3]. Since different NMs can react with DNA following different mechanisms, a wide range of tools have been proposed to detect and quantify different genotoxic effects; among them, the comet assay stands out.…”

Section: Introductionmentioning

confidence: 99%

The Comet Assay as a Tool to Detect the Genotoxic Potential of Nanomaterials

et al. 2019

View full text Add to dashboard Cite

The interesting physicochemical characteristics of nanomaterials (NMs) has brought about their increasing use and, consequently, their increasing presence in the environment. As emergent contaminants, there is an urgent need for new data about their potential side-effects on human health. Among their potential effects, the potential for DNA damage is of paramount relevance. Thus, in the context of the EU project NANoREG, the establishment of common robust protocols for detecting genotoxicity of NMs became an important aim. One of the developed protocols refers to the use of the comet assay, as a tool to detect the induction of DNA strand breaks. In this study, eight different NMs—TiO2NP (2), SiO2NP (2), ZnONP, CeO2NP, AgNP, and multi-walled carbon nanotubes (MWCNT)—were tested using two different human lung epithelial cell lines (A549 and BEAS-2B). The comet assay was carried out with and without the use of the formamidopyrimidine glycosylase (FPG) enzyme to detect the induction of oxidatively damaged DNA bases. As a high throughput approach, we have used GelBond films (GBF) instead of glass slides, allowing the fitting of 48 microgels on the same GBF. The results confirmed the suitability of the comet assay as a powerful tool to detect the genotoxic potential of NMs. Specifically, our results indicate that most of the selected nanomaterials showed mild to significant genotoxic effects, at least in the A549 cell line, reflecting the relevance of the cell line used to determine the genotoxic ability of a defined NM.

show abstract

Section: Introductionmentioning

confidence: 99%

The Comet Assay as a Tool to Detect the Genotoxic Potential of Nanomaterials

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This phenomenon of internalization would act as the first step of a potential NPs-cell nucleus interaction and, consequently, to DNA impairment. Therefore, Nanogenotoxicology is emerging as a specific research field covering such demands [13,14]. Among the different methodological approaches aiming to detect and quantify DNA damage, the micronucleus assay is very popular as it is well-established, reliable, accurate and reproducible.…”

Section: Introductionmentioning

confidence: 99%

Micronuclei Detection by Flow Cytometry as a High-Throughput Approach for the Genotoxicity Testing of Nanomaterials

et al. 2019

View full text Add to dashboard Cite

Thousands of nanomaterials (NMs)-containing products are currently under development or incorporated in the consumer market, despite our very limited understanding of their genotoxic potential. Taking into account that the toxicity and genotoxicity of NMs strongly depend on their physicochemical characteristics, many variables must be considered in the safety evaluation of each given NM. In this scenario, the challenge is to establish high-throughput methodologies able to generate rapid and robust genotoxicity data that can be used to critically assess and/or predict the biological effects associated with those NMs being under development or already present in the market. In this study, we have evaluated the advantages of using a flow cytometry-based approach testing micronucleus (MNs) induction (FCMN assay). In the frame of the EU NANoREG project, we have tested six different NMs—namely NM100 and NM101 (TiO2NPs), NM110 (ZnONPs), NM212 (CeO2NPs), NM300K (AgNPs) and NM401 (multi-walled carbon nanotubes (MWCNTs)). The obtained results confirm the ability of AgNPs and MWCNTs to induce MN in the human bronchial epithelial BEAS-2B cell line, whereas the other tested NMs retrieved non-significant increases in the MN frequency. Based on the alignment of the results with the data reported in the literature and the performance of the FCMN assay, we strongly recommend this assay as a reference method to systematically evaluate the potential genotoxicity of NMs.

show abstract

“…Co-culture systems involving inflammatory and target cells can contribute to discriminate between primary and secondary genotoxic mechanisms without the need of animal studies and have been already used with NMs [ 38 , 94 , 95 ]. The use of centromeric probes in combination with the MN assay can allow identified aneugenic materials, which are also assumed to have a threshold response [ 96 ].…”

Section: Recommendations For Designing Genotoxicity Studies Of Nanoma...mentioning

confidence: 99%

A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective

et al. 2022

View full text Add to dashboard Cite

The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.

show abstract

Towards a New Paradigm in Nano‐Genotoxicology: Facing Complexity of Nanomaterials’ Cellular Interactions and Effects

Cited by 11 publications

References 49 publications

The Comet Assay as a Tool to Detect the Genotoxic Potential of Nanomaterials

The Comet Assay as a Tool to Detect the Genotoxic Potential of Nanomaterials

Micronuclei Detection by Flow Cytometry as a High-Throughput Approach for the Genotoxicity Testing of Nanomaterials

A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective

Contact Info

Product

Resources

About