Toxicity of organotin compounds in primary cultures of rat cortical astrocytes

The neurotoxic organotin compounds trimethyl (TMT) and triethyltin (TET) ar e known to induce astrogliosis in vivo, which is indicated by an increased synthesis of glial fibrillary acidic protein (GFAP) in astrocytes. In contr ast, tributyltin (TBT) does not induce astrogliosis. The aim of this study was to investigate whether trialkyltin derivatives can induce an increased GFAP synthesis in astrocyte cultures in the absence of neurons and whether differences between the action of TMT, TET, and TBT can be detected. Primary cultures of rat cortical astrocytes from 2-day-old rats were grown in 96-well plates until confluency and then exposed to various concentratio ns of TMT, TET, and TBT for 40 h. Effects on basal cell functions were meas ured by colorimetric determination of cell protein contents and by assessme nt of viability by means of the MTT assay. An indirect sandwich ELISA for 9 6-well plates was used for quantitative measurements of the GFAP content of the cells. All three compounds induced a concentration-dependent cytotoxicity indicate d by parallel decreases of protein contents and MTT reduction. Half-maximum cytotoxic concentrations were 3 mu mol/L (TBT), 30 mu mol/L (TET), and 800 mu mol/L (TMT). Cellular GFAP contents were reduced in parallel to cytotox ic action but no increase in GFAP expression at subcytotoxic concentrations could be observed. Thus, the astrocytes were not able to respond to TMT or TET exposure by an increased synthesis of GFAP in the absence of neuronal signals.