Evidence map›Paper›PMID 40671358›Full record

ArticleMutagenesis2025

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

Stephen J Evans, Nynke Moelijker, Inger Brandsma, Michael J Burgum, Rosalie Elespuru, Giel Hendriks, Shareen H Doak

Abstract read
In one paragraph

Article in Mutagenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Stephen J EvansIn Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom.
Nynke MoelijkerToxys B.V., Leiden Bio Science Park, De Limes 7, 3042 DH Oegstgeest, The Netherlands.
Inger BrandsmaToxys B.V., Leiden Bio Science Park, De Limes 7, 3042 DH Oegstgeest, The Netherlands.ORCID 0000-0003-3257-2540
Michael J BurgumIn Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom.
Rosalie Elespuru3741 Thomas Point Road, Annapolis, MD 21403, United States.
Giel HendriksToxys B.V., Leiden Bio Science Park, De Limes 7, 3042 DH Oegstgeest, The Netherlands.ORCID 0000-0001-9506-5082
Shareen H DoakIn Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, Wales, United Kingdom.ORCID 0000-0002-6753-1987

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Evaluating the genotoxic potential of nanomaterials (NMs) presents unique challenges not associated with traditional toxicological assessment. A key question in any NM focused toxicity study is whether the material has reached the target cell and what its subsequent subcellular localization is. This current study aimed to assess the potential of a panel of industrially relevant NMs; 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, which are applied in the ToxTracker genotoxicity assay. Ultrastructural cellular analysis by transmission electron microscopy was undertaken following 100 μg/ml treatment with the test NMs 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 NMs (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, localized in membrane-bound vesicles within the cytoplasm. None of the internalized NMs promoted a genotoxic response in ToxTracker, and similarly, no DNA damage was observed by the materials not internalized. Interestingly, of the internalized NMs, only polystyrene caused a slight cytotoxic response at 100 μg/ml treatment (10% loss in cell viability). Of the NMs not internalized, 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 NM genotoxicity studies with cellular uptake analysis.

Indexed as

DNA DamageMouse Embryonic Stem CellsMutagensNanostructuresAnimalsCell SurvivalGoldMiceMicroscopy, Electron, TransmissionMutagenicity TestsOxidative StressSilicon DioxideSootTitaniumTumor Suppressor Protein p53Tungsten CompoundsGoldMutagensSilicon DioxideSootTitaniumtitanium dioxideTumor Suppressor Protein p53tungsten carbideTungsten CompoundsgenotoxicitynanomaterialToxTrackeruptake

Identifiers

PMID40671358
PMCPMC12534216

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.