Cited by 220Carcinogens and Genotoxicity AssessmentDrug-Induced Hepatotoxicity and ProtectionGene expression and cancer classification

Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification

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Jennen, Danyel G. J., Magkoufopoulou, Christina, Ketelslegers, Hans B., van Herwijnen, Marcel H. M., Kleinjans, Jos C. S., van Delft, Joost H. M.·2010·Toxicological Sciences

Abstract

Direct comparison of the hepatoma cell lines HepG2 and HepaRG has previously been performed by only evaluating a limited set of genes or proteins. In this study, we examined the whole-genome gene expression of both cell lines before and after exposure to the genotoxic (GTX) carcinogens aflatoxin B1 and benzo[a]pyrene and the nongenotoxic (NGTX) carcinogens cyclosporin A, 17beta-estradiol, and 2,3,7,8-tetrachlorodibenzo-para-dioxin for 12 and 48 h. Before exposure, this analysis revealed an extensive network of genes and pathways, which were regulated differentially for each cell line. The comparison of the basal gene expression between HepG2, HepaRG, primary human hepatocytes (PHH), and liver clearly showed that HepaRG resembles PHH and liver the most. After exposure to the GTX and NGTX carcinogens, for both cell lines, common pathways were found that are important in carcinogenesis, for example, cell cycle regulation and apoptosis. However, also clear differences between exposed HepG2 and HepaRG were observed, and these are related to common metabolic processes, immune response, and transcription processes. Furthermore, HepG2 performs better in discriminating between GTX and NGTX carcinogens. In conclusion, these results have shown that HepaRG is a more suited in vitro liver model for biological interpretations of the effects of exposure to chemicals, whereas HepG2 is a more promising in vitro liver model for classification studies using the toxicogenomics approach. Although, it should be noted that only five carcinogens were used in this study.

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Crossref · 10.1093/toxsci/kfq026

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  • Commercial cell lines including HepG2/C3A provide a more stable, easy-to-handle and readily available source of human cells for in vitro studies on liver function and general mechanisms of toxicity.

    “Commercial cell lines including HepG2/C3A provide a more stable, easy-to-handle and readily available source of human cells for in vitro studies on liver function and general mechanisms of toxicity [58,59].”

    From A liver-on-a-chip platform with bioprinted hepatic spheroids (2016) · cites this paper as [58]

    The paper’s Abstract describes HepG2 as easy to handle compared with primary human hepatocytes and as a frequently used model for toxicogenomics studies. It does not establish that these cell lines are more stable or readily available, and it does not address HepG2/C3A specifically. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Authors
Jennen, D. G. J., Magkoufopoulou, C., Ketelslegers, H. B., van Herwijnen, M. H. M., Kleinjans, J. C. S., & van Delft, J. H. M.
Affiliations
Maastricht University (NL)
Corresponding author
Jennen, Danyel G. J.
Venue
Toxicological Sciences
Published
2010-01-27
Volume
115
Issue
1
Pages
66-79
ISSN
  • 1096-0929 (ISSN-L)
  • 1096-6080
OpenAlex
W2169675397
Cited by
220
References
42
Citations by year
2026: 6 · 2025: 10 · 2024: 15 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 14 · 2019: 14 · 2018: 14 · 2017: 7 · 2016: 24 · 2015: 14 · 2014: 19 · 2013: 16 · 2012: 21
FWCI
5.74
Type
journal article
Language
en
Open access
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • European Commission (LSHB-CT-2006-037712)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • Stichting voor de Technische Wetenschappen (MFA6809)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
HepG2 cells, HepaRG cells, hepatoma cell lines, in vitro liver models, carcinogenicity classification, genotoxic carcinogens, non-genotoxic carcinogens, aflatoxin B1, benzo[a]pyrene, cyclosporine, estradiol, 2,3,7,8-tetrachlorodibenzo-p-dioxin, whole-genome gene expression, toxicogenomics, primary human hepatocytes, cell cycle regulation, apoptosis, chemical hazard identification
MeSH terms
Carcinogens, Humans, Predictive Value of Tests, Carcinogenicity Tests, Gene Expression Regulation, Neoplastic, Risk Assessment, Gene Expression Profiling, Hepatocytes, Genomics, Animal Use Alternatives, Hep G2 Cells

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