Inhibition of protein synthesis by trimethyltin

The effects of trimethyltin chloride (TMT) on protein synthesis, measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material, were investigated in mice. One hour after intraperitoneal administration of a 3.0 mg/kg dose, TMT decreased brain protein synthesis by 47% and also caused a significant decrease (4.2 degrees C) in body temperature. When hypothermia was prevented by maintaining the animals at 35 degrees C, TMT decreased protein synthesis by 20%. Twenty-four hours following administration of TMT, protein synthesis was decreased in brain and liver; however, only a reduction of brain protein synthesis was observed at 48 hr. No hypothermia was present at either time point. A regional study in brain showed that at 24 and 48 hr after TMT administration, protein synthesis was decreased by 18-23% in cerebral cortex and hippocampus but not in cerebellum. TMT also inhibited protein synthesis in vitro in mouse brain homogenates with an IC50 of about 100 microM. Neither SnCl2, nor dimethyltin or monomethyltin had any effect on protein synthesis in vitro. These results suggest that, as for other neurotoxicants such as methyl mercury or acrylamide, inhibition of protein synthesis might be involved in TMT neurotoxicity.