Performance of Comet and Micronucleus Assays in Metabolic Competent HepaRG Cells to Predict In Vivo Genotoxicity

Genetic toxicity information is critical for the safety assessment of all xenobiotics. In the absence of carcinogenicity data, genetic toxicity studies may be used to draw conclusions about the car-cinogenicity potential of chemicals. However, current in vitro as-says have many limitations as they produce a high rate of irrele-vant positive data and possible false negative data due to the weak-ness of the in vitro models used. Based on the knowledge that the majority of human genotoxic carcinogens require metabolic acti-vation to become genotoxic, it is necessary to develop in vitro cell models that mimic human liver metabolism to replace the use of liver S9 fraction, which, though helpful for predicting the poten-tial carcinogenicity of chemicals in rodents, is questionable in hu-mans. We therefore investigate whether the recently described hu-man hepatoma HepaRG cells, which express the major character-istics of liver functions similarly to primary human hepatocytes