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A New Human Hepatoma Cell Line to Study Repeated Cell Toxicity

Nicolas Fabre, Elsa Arrivet, Françoise Paillard, Valérie Wibaut-Berlaimont, Nicole Bichet, Nigel O. Roome, Annick Prenez and Joan-Albert Vericat

Early toxicity screening of new drugs is performed to select candidates for development. Many cell models are used to assess basic cytotoxicity and to show a good correlation with acute toxicity. However, their correlation with chronic in vivo exposure is inadequate. The new hepatoma cell line (HBG BC2) possesses the capacities of being reversibly differentiated in vitro, and of maintaining a relatively higher metabolic rate when in the differentiated phase (3 weeks) as compared to Hep G2 cells. MTT reduction was used to evaluate the toxicity of propranolol, perhexiline, aspirin and paracetamol, after both single and repeated treatments (three times a week for 2 weeks). Under conditions of repeated treatment, cytotoxicity was observed at lower doses when compared with single administration. Moreover, the first non-toxic doses were in the same range as plasma concentrations measured in humans during therapeutic use. Our results suggest that the new human hepatoma HBG BC2 cell line may be of interest for the evaluation of cell toxicity under repeated treatment conditions.