Toxicity Profiles of Four Metals and 17 Xenobiotics in the Human Hepatoma Cell Line HepG2 and the Protozoa Tetrahymena pyriformis-A Comparison

We performed an interspecies comparison for the human hepatoma cell line HepG2 and the eukaryotic single cell organism Tetrahymena pyriformis (T. pyriformis) for 17 xenobiotics with diverse structures and four metals. The cytotoxicity was assessed by four different cell viability assays (3-[ 4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction (MTT), neutral red uptake (NRU), resazurin dye (AlamarBlue), 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM)) for the HepG2 and by cell count and MTT for T. pyriformis. For HepG2 cells, the results revealed interassay variations depending on the compound. The highest assay conformity was found for the metal Hg2+ and the fungicide prochloraz. The AlamarBlue assay was the most sensitive assay according to low-effect concentrations. By contrast, the NRU assay was comprised of more frequent whole concentration response relationships and was more susceptible to EC50. For T. pyriformis the EC50 values of the two applied assays displayed a high conformity (R-2 = 0.97). Comparing the EC50 values obtained by the MTT assay for the two cell models, a direct correlation was absent for the xenobiotics and only present for the metals (Cd2+, Cu2+, and Ni2+). Moreover, the protozoa T. pyriformis displayed a 20 times higher sensitivity than the cell line. The highest interspecies difference of three log degrees was obtained for the polycyclic aromatic hydrocarbon fluoranthene. In addition, a correlation of the EC50 values and octanol-water partition coefficient (log K-OW) of the xenobiotics was performed. No correlation was found for HepG2, and a weak one for T. pyriformis. Interestingly, the interspecies difference of logarithmized EC50 correlated positive with the log K-OW (R-2 = 0.65). In conclusion, to obtain reliable evidence for human cytotoxicity, more than one viability/cytotoxicity assay had to be applied for cell lines. Second, the human hepatoma cell line was less affected by the organic compounds than the eukaryotic single-cell organism and was also less dependent on the log K-OW of the xenobiotic. (c) 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 171-186, 2011.