Cytotoxic potency of trialkyltins to C6 glioma cells in vitro: impact of exposure conditions.
Because of a possible role of astrocytes in trialkyltin-induced neurotoxicity in vivo various studies have been performed using cultures of astrocytes or glioma cells in vitro. With respect to cytotoxic potencies of trialkyltins these studies gave rather divergent results. Therefore the aim of the present study was to clarify whether variations of experimental conditions could be responsible for the differences of the cytotoxic activities of trimethyltin (TMT), triethyltin (TET) and tributyltin (TBT). Experiments were performed with rat C6 glioma cells. Toxicity was determined by measuring the reduction of the cell protein content. Cultures of proliferating and growth-arrested cells did not differ in their sensitivity. Exposure duration (1-72 h) had a strong but differing influence on the cytotoxic potency of the trialkyltins. After short exposure times the potencies differed largely (TMT < TET < TBT), whereas they became more and more similar with increasing exposure duration. The potency-time relationships for TMT and TET could be described by the equation: EC50 = k x t(-n), while for TBT an incipient value (EC50, infinity) had to be included: EC50 = EC50, infinity + k x t(-n). Addition of serum albumin to the culture medium decreased the cytotoxic potency of the trialkyltins. However, the impact of protein binding on their bioavailability was relatively low. The cytotoxic potency of the alkyltins was not dependent on the concentration of C6 cells. Taken together, neither differences in exposure conditions nor in the proliferative status of the cells are sufficient to account for the discrepancies in published results for trialkyltin cytotoxicity to astrocytes. Instead they may--at least partially--be explained by differing sensitivities of the endpoints used. Furthermore, C6 glioma cells respond considerably more sensitively to trialkytins than primary astrocytes, which questions their applicability as models for astrocyte toxicity.
Seibert
H
H
Institut für Toxikologie und Pharmakologie für Naturwissenschaftler, Universitätsklinikum Schleswig-Holstein, Kiel, Germany. seibert@toxi.uni-kiel.de
Mörchel
S
S
Gülden
M
M
D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy*; D011485:Protein Binding; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*
D014220:Trialkyltin Compounds; D012710:Serum Albumin, Bovine