Cytotoxicity assessment of three therapeutic agents, cyclosporin-A, cisplatin and doxorubicin, with the ciliated protozoan Tetrahymena pyriformis

Cyclosporin-A, a drug possessing potent immunosuppressive properties, is used to prevent allograft rejection. Cisplatin and doxorubicin are two of the pharmaceutical drugs most widely used in cancer chemotherapy. In this study, the cytotoxicological impact of these three therapeutic agents was determined using bioassays performed with a unicellular eukaryote, the ciliated protozoan Tetrahymena pyriformis. For this purpose we used the population growth impairment test and the non-specific esterase activities test. We also examined some morphological effects. The results show that these three agents are toxic towards T. pyriformis. A concentration-dependent inhibitory effect on the cell proliferation rate of T. pyriformis populations was found for the three drugs. The IC50 values were, respectively, 42.03 +/- 4.64, 124.37 +/- 7.47 and 74.62 +/- 6.12 muM for cyclosporin-A, cisplatin and doxorubicin. Non-specific esterase activities were also modified compared with untreated cells. The IC50 values were, respectively, 88.32 +/- 8.35 and 44.61 +/- 3.33 muM for cisplatin and doxorubicin. Exposure of T. pyriformis to these drugs caused the prompt appearance of digestive vacuoles concentrating particulate elements. This phenomenon was more pronounced at higher concentrations. We also observed deformed cells with cisplatin. T. pyriformis bioassays can offer an alternative in vitro method to cell cultures for the risk assessment of potentially toxic drugs. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.