Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells

Food Chem Toxicol. 2020 Jun:140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.


The conventional approach for testing the genotoxic potential of chemicals in vitro includes a battery of bacterial and mammalian mutagenicity tests. Toxicogenomics analyses may provide information about DNA-damaging properties of test compounds but are not routinely used for identification of a genotoxic potential. In this study, metabolically active human HepaRG hepatocarcinoma cells were exposed to five food-relevant genotoxic carcinogens. Transcriptomic responses were analyzed using RNA sequencing technology and validated by real-time polymerase chain reaction. Biostatistical approaches revealed a characteristic transcript signature of 37 differentially expressed genes, which were commonly regulated by the test chemicals. Specificity of the transcript signature was confirmed by using non-genotoxic carcinogens as comparators. Pathway analyses showed that the obtained transcript signature was closely related to DNA damage response and p53 activation. In conclusion, we have established a characteristic transcript marker pattern to monitor genotoxicity in human HepaRG cells, and to distinguish genotoxic from non-genotoxic carcinogens. Our analyses underline that a common response related to DNA damages response, cell cycle alterations and cell death is initiated in HepaRG cells upon exposure to genotoxic compounds and allows for the identification of a common transcriptomic signature for genotoxic stress.

Keywords: Aflatoxin; Food toxicology; Gene expression; HepaRG; Hepatotoxicity; Toxicogenomics; benzo[a]pyrene.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • DNA Damage
  • Food Contamination / analysis*
  • Humans
  • Liver Neoplasms / genetics*
  • Mutagens / toxicity*
  • RNA, Messenger / genetics
  • Sequence Analysis, RNA
  • Transcriptome*
  • Tumor Suppressor Protein p53 / metabolism


  • Mutagens
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53