ArticleArchives of toxicology2023
High-throughput micronucleus assay using three-dimensional HepaRG spheroids for in vitro genotoxicity testing.
Article in Archives of toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Advancing genotoxicity assessment with transcriptomic biomarkers: from 2D to 3D HepaRG spheroid models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Optimization of Cytokinesis-Block Micronucleus Assay for Clastogenic Risk Assessment of Silver-Containing Nanomaterials.Nanomaterials (Basel, Switzerland) · 2026Article
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Mutagenicity of EAT-positive NDSRIs in HepaRG spheroids.NAM journal · 2026Article
- Rapid detection of genotoxicity employing an engineered high-sensitivity and tight SOS-response biosensor inSynthetic and systems biotechnology · 2026Article
- Flow Cytometric Determination of Micronucleus Frequency.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Interpretation of in vitro concentration-response data for risk assessment and regulatory decision-making: Report from the 2022 IWGT quantitative analysis expert working group meeting.Environmental and molecular mutagenesis · 2025Review
- Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cell models.Regulatory toxicology and pharmacology : RTP · 2025Article
- Development of a TK6-derived cell line expressing four human cytochrome P450s for genotoxicity testing.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
- Comparative DNA damage induced by eight nitrosamines in primary human and macaque hepatocytes.Chemico-biological interactions · 2025Article
- Integration of the rat liver micronucleus assay into a 28-day treatment protocol: testing the genotoxicity of 4 small-molecule nitrosamines with different carcinogenic potencies and tumor target specificities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Article
- Oxide-Perovskites for Automotive Catalysts Biotransform and Induce Multicomponent Clearance and Hazard.ACS nano · 2024Article
- 3D spheroid HepaRG and fluorescent biphasic tracer for CYP3A4-mediated antibiotic interaction monitoring in sepsis.Analytical and bioanalytical chemistry · 2024Article
- Evaluating the mutagenicity of N-nitrosodimethylamine in 2D and 3D HepaRG cell cultures using error-corrected next generation sequencing.Archives of toxicology · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Genotoxicity assessment of eight nitrosamines using 2D and 3D HepaRG cell models.Archives of toxicology · 2023Article
- Comparison of two protocols for the generation of iPSC-derived human astrocytes.Biological procedures online · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The in vitro micronucleus (MN) assay is a component of most test batteries used in assessing potential genotoxicity. Our previous study adapted metabolically competent HepaRG cells to the high-throughput (HT) flow-cytometry-based MN assay for genotoxicity assessment (Guo et al. in J Toxicol Environ Health A 83:702-717, 2020b, https://doi.org/10.1080/15287394.2020.1822972 ). We also demonstrated that, compared to HepaRG cells grown as two-dimensional (2D) cultures, 3D HepaRG spheroids have increased metabolic capacity and improved sensitivity in detecting DNA damage induced by genotoxicants using the comet assay (Seo et al. in ALTEX 39:583-604, 2022, https://doi.org/10.14573/altex.22011212022 ). In the present study, we have compared the performance of the HT flow-cytometry-based MN assay in HepaRG spheroids and 2D HepaRG cells by testing 34 compounds, including 19 genotoxicants or carcinogens and 15 compounds that show different genotoxic responses in vitro and in vivo. 2D HepaRG cells and spheroids were exposed to the test compounds for 24 h, followed by an additional 3- or 6-day incubation with human epidermal growth factor to stimulate cell division. The results demonstrated that HepaRG spheroids showed generally higher sensitivity in detecting several indirect-acting genotoxicants (require metabolic activation) compared to 2D cultures, with 7,12-dimethylbenzanthracene and N-nitrosodimethylamine inducing higher % MN formation along with having significantly lower benchmark dose values for MN induction in 3D spheroids. These data suggest that 3D HepaRG spheroids can be adapted to the HT flow-cytometry-based MN assay for genotoxicity testing. Our findings also indicate that integration of the MN and comet assays improved the sensitivity for detecting genotoxicants that require metabolic activation. These results suggest that HepaRG spheroids may contribute to New Approach Methodologies for genotoxicity assessment.
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