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Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro

Stephen Evans Orcid Logo, Nynke Moelijker, Inger Brandsma Orcid Logo, Michael Burgum, Rosalie Elespuru, Giel Hendriks Orcid Logo, shareen Doak

Mutagenesis, Volume: 40, Issue: 4, Pages: 550 - 559

Swansea University Authors: Stephen Evans Orcid Logo, Michael Burgum, shareen Doak

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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...

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Published in: Mutagenesis
ISSN: 0267-8357 1464-3804
Published: Oxford University Press (OUP) 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa69838
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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 &#x3BC;g/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 &#x3BC;g/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 &#x3BC;g/ml treatment (10% loss in cell viability). Of the nanomaterials not internalised, cytotoxicity was observed in mES cells treated with 100 &#x3BC;g/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. 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spelling 2025-10-29T15:27:28.6795569 v2 69838 2025-06-27 Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro cfca981bdfb8492873a48cc1629def9a 0000-0002-5352-9800 Stephen Evans Stephen Evans true false d3fe156a5ee169e586b8bad6ae4cb1d8 Michael Burgum Michael Burgum true false 8f70286908f67238a527a98cbf66d387 shareen Doak shareen Doak true false 2025-06-27 MEDS 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. Journal Article Mutagenesis 40 4 550 559 Oxford University Press (OUP) 0267-8357 1464-3804 nanomaterial, genotoxicity, ToxTracker, uptake 17 7 2025 2025-07-17 10.1093/mutage/geaf013 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) The authors would like to acknowledge that this research has received funding from The Health and Environmental Sciences Institute Genetic Toxicology Technical Committee. 2025-10-29T15:27:28.6795569 2025-06-27T14:57:33.7209190 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Stephen Evans 0000-0002-5352-9800 1 Nynke Moelijker 2 Inger Brandsma 0000-0003-3257-2540 3 Michael Burgum 4 Rosalie Elespuru 5 Giel Hendriks 0000-0001-9506-5082 6 shareen Doak 7 69838__35495__57f54f6ab2e74016b2a34617243a5709.pdf 69838.VOR.pdf 2025-10-29T15:22:58.2286097 Output 1312849 application/pdf Version of Record true © 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). true eng https://creativecommons.org/licenses/by/4.0/
title Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
spellingShingle Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
Stephen Evans
Michael Burgum
shareen Doak
title_short Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
title_full Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
title_fullStr Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
title_full_unstemmed Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
title_sort Understanding the cellular uptake and genotoxic potential of industrial relevant nanomaterials utilizing electron microscopy and the ToxTracker assay in vitro
author_id_str_mv cfca981bdfb8492873a48cc1629def9a
d3fe156a5ee169e586b8bad6ae4cb1d8
8f70286908f67238a527a98cbf66d387
author_id_fullname_str_mv cfca981bdfb8492873a48cc1629def9a_***_Stephen Evans
d3fe156a5ee169e586b8bad6ae4cb1d8_***_Michael Burgum
8f70286908f67238a527a98cbf66d387_***_shareen Doak
author Stephen Evans
Michael Burgum
shareen Doak
author2 Stephen Evans
Nynke Moelijker
Inger Brandsma
Michael Burgum
Rosalie Elespuru
Giel Hendriks
shareen Doak
format Journal article
container_title Mutagenesis
container_volume 40
container_issue 4
container_start_page 550
publishDate 2025
institution Swansea University
issn 0267-8357
1464-3804
doi_str_mv 10.1093/mutage/geaf013
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
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description 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.
published_date 2025-07-17T05:29:14Z
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