Evidence map›Paper›PMID 31332230›Full record

ArticleScientific reports2019

Three-dimensional HepaRG spheroids as a liver model to study human genotoxicity in vitro with the single cell gel electrophoresis assay.

Marion Mandon, Sylvie Huet, Estelle Dubreil, Valérie Fessard, Ludovic Le Hégarat

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.4field-weighted citation impact, top 6% of its field
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

37 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. 3D Liver Models for Genotoxicity Testing.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  3. Application of the Comet Assay in Advanced In Vitro Models.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Transferability and Reproducibility of the HepaRG CometChip Assay.Environmental and molecular mutagenesis · 2025
    Article
  5. Article
  6. Article
  7. Advancing Environmental ToxicologyEnvironment & health (Washington, D.C.) · 2024
    Review
  8. Article
  9. Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024
    Review
  10. Extended lifespan and improved genome stability in HepaRG-derived cell lines through reprogramming by high-density stress.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Assessment of the genotoxicity of acrylamide.EFSA journal. European Food Safety Authority · 2022
    Article
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

5 authors at 1 institution in 1 country.

Marion MandonANSES, French Agency for Food, Environmental and Occupational Health and Safety, Fougères Laboratory, Toxicology of contaminants unit, 10 B rue Claude Bourgelat, Fougères, 35306, France.
Sylvie HuetANSES, French Agency for Food, Environmental and Occupational Health and Safety, Fougères Laboratory, Toxicology of contaminants unit, 10 B rue Claude Bourgelat, Fougères, 35306, France.
Estelle DubreilANSES, French Agency for Food, Environmental and Occupational Health and Safety, Fougères Laboratory, Analysis of residues and contaminants unit, 10 B rue Claude Bourgelat, Fougères, 35306, France.
Valérie FessardANSES, French Agency for Food, Environmental and Occupational Health and Safety, Fougères Laboratory, Toxicology of contaminants unit, 10 B rue Claude Bourgelat, Fougères, 35306, France.
Ludovic Le HégaratANSES, French Agency for Food, Environmental and Occupational Health and Safety, Fougères Laboratory, Toxicology of contaminants unit, 10 B rue Claude Bourgelat, Fougères, 35306, France. ludovic.lehegarat@anses.fr.ORCID http://orcid.org/0000-0003-3494-4109
Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many efforts have been made in the last 30 years to develop more relevant in vitro models to study genotoxic responses of drugs and environmental contaminants. While 2D HepaRG cells are one of the most promising models for liver toxicology, a switch to 3D cultures that integrate both in vivo architecture and cell-cell interactions has occurred to achieve even more predictive models. Preliminary studies have indicated that 3D HepaRG cells are suitable for liver toxicity screening. Our study aimed to evaluate the response of HepaRG spheroids exposed to various genotoxic compounds using the single cell gel electrophoresis assay. HepaRG spheroids were used at 10 days after seeding and exposed for 24 and 48 hours to certain selected chemical compounds (methylmethansulfonate (MMS), etoposide, benzo[a]pyrene (B[a]P), cyclophosphamide (CPA), 7,12-dimethylbenz[a]anthracene (DMBA), 2-acetylaminofluorene (2-AAF), 4-nitroquinoline (4-NQO), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), acrylamide, and 2-4-diaminotoluene (2,4-DAT)). After treatment, the comet assay was performed on single cell suspensions and cytotoxicity was determined by the ATP assay. Comet formation was observed for all compounds except IQ, etoposide and 2,4-DAT. Treatment of spheroids with rifampicin increased CYP3A4 activity, demonstrating the metabolic capacity of HepaRG spheroids. These data on genotoxicity in 3D HepaRG spheroids are promising, but further experiments are required to prove that this model can improve the predictivity of in vitro models to detect human carcinogens.

Indexed as

Activation, MetabolicCell LineComet AssayCytochrome P-450 Enzyme SystemDNA DamageHepatocytesHumansMutagensSpheroids, CellularCytochrome P-450 Enzyme SystemMutagens

Identifiers

PMID31332230
PMCPMC6646340
OpenAlexW2963515744

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.