Inhibition of RNA and protein synthesis in isolated cerebellar cells by in vitro and in vivo methyl mercury.

Abstract

Cerebellar perikarya isolated from neonatal rats were exposed to 0-20 microM methyl mercury to simultaneously compare the effect on RNA and protein synthesis. Although 50% inhibition was found at approximately 8 microM for both [3H]uridine and [3H]phenylalanine incorporation, lower concentrations of methyl mercury produced 10-15% greater inhibition of RNA than protein synthesis. In vivo methyl mercury experiments also indicated a greater sensitivity of RNA synthesis in isolated cerebellar perikarya. The observed inhibition of RNA synthesis was not caused by a defect in cellular [3H]uridine uptake or by increased degradation of RNA. Both of these activities were altered by less than 10% at concentrations of methyl mercury that produced greater than 60% inhibition of RNA synthesis. Experiments showing that the specific activity of cerebellar cell RNA synthesis peaks and remains high between 4 and 10 d of age, whereas the specific activity of protein synthesis declines rapidly emphasize the potential importance of transcriptional perturbation in neonatal rats.