GLUTATHIONE MODIFIES THE TOXICITY OF TRIETHYLTIN AND TRIMETHYLTIN IN C6 GLIOMA-CELLS

It has been demonstrated that exposure to mercury or cadmium compounds causes alterations in the glutathione system in a model glial cell li ne, C6. Here we report that two organic tin compounds, triethyltin (TE T) and trimethyltin (TMT), are also toxic to these cells with EC50 val ues for cell death of c. 0.02 mu M and 0.8 mu M respectively. Exposure for 24 h to either of these compounds at sub-toxic concentrations cau sed increases in the amount of reduced glutathione (GSH) per cell. Inc reases in glutathione-S-transferase enzyme activity were also demonstr ated after TET or TMT exposure. This suggests that glutathione increas es occur in glial cells after toxic insults below that required to cau se cell death, possibly acting as a protective mechanism. To test whet her GSH plays a role in organotin-induced cell death we manipulated GS H in the culture media or via intracellular GSH and looked at the effe cts on sensitivity to TET or TMT toxicity. Adding GSH to the culture m edia did not protect the cells. Depletion of intracellular GSH with bu thionine-[S,R] sulphoximine did not alter cytotoxicity of TET or TMT. However, pre-treatment with (-)-2-oxo-4-thiazolidine carboxylic acid ( OTC), which increases intracellular GSH levels, protected the cells ag ainst both compounds. The EC50 for TMT was increased from 0.77 to 1.8 mu M, a 2.3-fold shift, whereas the EC50 for TET was increased > 20-fo ld, from 0.022 to 0.47 mu M. One interpretation of these results is th at GSH protects cells against the toxicity of organic tin compounds wi thout reacting directly with them to any significant extent. Under con ditions where GSH is depleted, additional protective mechanisms may be active.