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 (R² = 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 (R² = 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. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 171–186, 2011.