Inhibition of protein synthesis by N-methyl-N-nitrosourea in vivo.
1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2-3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyribosomes was found in adult rat brains although N-methyl-N-nitrosourea inhibited cerebral and hepatic protein synthesis to a similar extent. In weanling rats N-methyl-N-nitrosourea caused a shift in the cerebral polyribosome profile similar to but less marked than that in rat liver. 3. Reaction of polyribosomal RNA with N-[(14)C]methyl-N-nitrosourea in vitro did not lead to a disaggregation of polyribosomes although the amounts of 7-methylguanine produced were up to twenty times higher than those found after administration of sublethal doses in vivo. 4. It was concluded that changes in the polyribosome profile induced by N-methyl-N-nitrosourea may reflect the mechanism of inhibition of protein synthesis rather than being a direct consequence of the methylation of polyribosomal mRNA.
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D005260:Female; D006147:Guanine / Q000032:analysis; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011132:Polyribosomes / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D012260:Ribonucleases / Q000494:pharmacology; D012270:Ribosomes / Q000187:drug effects
D002250:Carbon Radioisotopes; D009419:Nerve Tissue Proteins; D009607:Nitrosourea Compounds; D006147:Guanine; D012260:Ribonucleases; D007930:Leucine