Comparison of HepG2 and HepaRG by Whole-Genome Gene Expression Analysis for the Purpose of Chemical Hazard Identification

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.

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

“…In particular, they are able to express numerous P450 cytochromes, allowing the performance of many normal metabolic liver functions such as the production of phase I and II enzymes and transmembrane transport proteins, unlike other hepatocyte cell lines such as HepG2 (Guillouzo et al 2007;Kanebratt and Andersson 2008;Turpeinen et al 2009;Jennen et al 2010). …”

Lophirones B and C prevent aflatoxin B1-induced oxidative stress and DNA fragmentation in rat hepatocytes

“…Studies have shown that AFB 1 alters cell cycle and apoptosis-signalling pathways in liver cell models (Ellinger-Ziegelbauer et al 2004;Li et al 2004;Tilton et al 2005;Josse et al 2012). In particular, the p53-related genes are upregulated, leading to the induction of target genes involved in cell-cycle arrest, apoptosis and stimulation of DNA repair activity (Jennen et al 2010;Josse et al 2012).…”

In Vitro, In Vivo Comparison of Cyclosporin A Induced Hepatic Protein Expression Profiles

“…The hepatotoxic properties of chemicals and drugs are usually analyzed in in vivo repeated-dose toxicity tests, which involve a high number of laboratory animals. To reduce the amount of laboratory animals, alternative in vitro models are currently developed and their screening properties evaluated [1][2][3]. Ideally these in vitro models reflect the in vivo toxicological response.…”