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

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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

DOI 10.1093/toxsci/kfq026

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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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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.
ORCID: Jennen, Danyel G. J.
Magkoufopoulou, Christina
Kleinjans, Jos C. S.
Venue: Toxicological Sciences
Publisher: Oxford University Press (OUP)
Published: 2010-01-27
Volume: 115
Issue: 1
Pages: 66-79
ISSN: 1096-0929 (ISSN-L)
1096-6080
DOI: 10.1093/toxsci/kfq026
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: bronze
doi.org
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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Comparison of HepG2 and HepaRG by Whole-Genome Gene Expression Analysis for the Purpose of Chemical Hazard Identification

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