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Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
,
Nynke Moelijker,
Inger Brandsma ,
Michael Burgum,
Rosalie Elespuru,
Giel Hendriks ,
shareen Doak
Mutagenesis, Volume: 40, Issue: 4, Pages: 550 - 559
Swansea University Authors:
Stephen Evans , Michael Burgum, shareen Doak
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© The Author(s) 2025. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY).
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DOI (Published version): 10.1093/mutage/geaf013
Abstract
Evaluating genotoxic potential of nanomaterials presents unique challenges not associated with traditional toxicological assessment. The exceptional properties and complexities of these nanomaterials require additional considerations and protocol modifications to assess and fully interpret genotoxic...
| Published in: | Mutagenesis |
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| ISSN: | 0267-8357 1464-3804 |
| Published: |
Oxford University Press (OUP)
2025
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa69838 |
| Abstract: |
Evaluating genotoxic potential of nanomaterials presents unique challenges not associated with traditional toxicological assessment. The exceptional properties and complexities of these nanomaterials require additional considerations and protocol modifications to assess and fully interpret genotoxicity potential. A key question in any nanomaterial focused toxicity study is whether the material has reached the target cell and what its subsequent sub-cellular localisation is. This current study aimed to assess the potential of a panel of industrial relevant nanomaterials; TiO2-NM102, TiO2-NM105, TiO2-E171, silica, polyethylene, polystyrene, carbon black, Gold nanorods, tungsten carbide/cobalt and tungsten carbide, to undergo cellular uptake in mouse embryonic stem cells (mES) that are applied in the ToxTracker genotoxicity assay. Ultrastructural cellular analysis by transmission electron microscopy (TEM) was undertaken following 100 μg/ml treatment with the test nanomaterials for 24 h, any observed uptake was confirmed by energy dispersive X-ray spectroscopy. Induction of DNA damage, cytotoxicity, p53 activation, protein stress, and oxidative stress was evaluated by the ToxTracker assay following 24 h treatment with the test nanomaterials (0-100 μg/ml) in the absence of S9. TiO2-NM105, silica, polystyrene carbon black and tungsten carbide were all shown to undergo cellular uptake, localised in membrane bound vesicles within the cytoplasm. None of the internalised nanomaterials promoted a genotoxic response in ToxTracker, similarly no DNA damage was observed by the materials not internalised. Interestingly, of the internalised nanomaterials only polystyrene caused a slight cytotoxic response at 100 μg/ml treatment (10% loss in cell viability). Of the nanomaterials not internalised, cytotoxicity was observed in mES cells treated with 100 μg/ml TiO2-NM102 (15%), polyethylene (15%), Gold nanorods (35%) and tungsten carbide/cobalt (45%). In summary this study demonstrated that TiO2-NM105, silica, polystyrene carbon black and tungsten carbide are non-genotoxic in vitro despite undergoing cell uptake in the ToxTracker cells. A continued focus is needed to supplement nanomaterial genotoxicity studies with cellular uptake analysis. |
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| Keywords: |
nanomaterial, genotoxicity, ToxTracker, uptake |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
The authors would like to acknowledge that this research has received funding from The Health and Environmental Sciences Institute Genetic Toxicology Technical Committee. |
| Issue: |
4 |
| Start Page: |
550 |
| End Page: |
559 |