Inhibition of RNA and protein synthesis in isolated cerebellar cells by in vitro and in vivo methyl mercury.
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.
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D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D008767:Methylmercury Compounds / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014529:Uridine / Q000378:metabolism
D008767:Methylmercury Compounds; D011506:Proteins; D012313:RNA; D014529:Uridine