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 IC(50) values were, respectively, 42.03+/-4.64, 124.37+/-7.47 and 74.62+/-6.12 microM for cyclosporin-A, cisplatin and doxorubicin. Non-specific esterase activities were also modified compared with untreated cells. The IC(50) values were, respectively, 88.32+/-8.35 and 44.61+/-3.33 microM 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.
Bonnet
Jean-Louis
JL
Laboratoire de Biologie Cellulaire, Faculté de Pharmacie, Université d'Auvergne, 28, place Henri-Dunant, BP38, 63001 Clermont-Ferrand Cedex 1, France. J-Louis.BONNET@u-clermont1.fr
Dusser
Martine
M
Bohatier
Jacques
J
Laffosse
Josée
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D001681:Biological Assay; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D016572:Cyclosporine / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D004351:Drug Resistance; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000633:toxicity*; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D004317:Doxorubicin; D016572:Cyclosporine; D002945:Cisplatin