Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver.
Engineered nanomaterials
Genotoxicity
In vitro liver models
Nanotoxicology
Physiologically relevant exposure
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
28 Jun 2021
28 Jun 2021
Historique:
received:
23
03
2021
accepted:
13
06
2021
entrez:
29
6
2021
pubmed:
30
6
2021
medline:
1
12
2021
Statut:
epublish
Résumé
With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.
Sections du résumé
BACKGROUND
BACKGROUND
With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO
RESULTS
RESULTS
Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO
CONCLUSION
CONCLUSIONS
In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.
Identifiants
pubmed: 34183029
doi: 10.1186/s12951-021-00938-w
pii: 10.1186/s12951-021-00938-w
pmc: PMC8240362
doi:
Substances chimiques
Albumins
0
Cytokines
0
Urea
8W8T17847W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
193Subventions
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/R001375/1
Pays : United Kingdom
Organisme : Horizon 2020 Framework Programme ()
ID : 760813
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