INHIBITION OF PROTEIN SYNTHESIS IN MAMMALIAN CELL-FREE SYSTEMS BY CHLORAMPHENICOL.
Chloramphenicol can inhibit protein synthesis in mammalian cell-free systems as effectively as it inhibits protein synthesis in analogous microbial systems. Significant inhibition in mammalian systems was obtained only when protein synthesis was stimulated by the addition of template RNA to the system, there being comparatively little inhibition of protein synthesis by ribosomes in the absence of stimulatory RNA. It is postulated that chloramphenicol may inhibit the function of messenger or template RNA by successfully competing for ribosomal binding sites, thereby preventing the attachment of RNA to ribosomes. The apparent discrepancy in the sensitivity of mammalian and microbial cells to chloramphenicol may be related to differences in turnover or stability of ribosomal template RNA rather than to intrinsic differences in mechanism of protein synthesis. These observations are in accord with the suggestion that protein synthesis in intact mammalian cells may be susceptible to chloramphenicol inhibition only at the time that new messenger or template RNA is being deposited on ribosomes and that more mature cells may be resistant because informative RNA already deposited on ribosomes is not accessible to chloramphenicol inhibition. The inhibitory effect of chloramphenicol on protein synthesis in proliferating cells may be an important factor in hematologic toxicity attributable to chloramphenicol.
D000818:Animals; D002247:Carbon Isotopes; D002474:Cell-Free System; D002701:Chloramphenicol; D007930:Leucine; D010600:Pharmacology; D010649:Phenylalanine; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012313:RNA; D012333:RNA, Messenger; D011817:Rabbits; D012106:Research; D012156:Reticulocytes; D012270:Ribosomes
D002247:Carbon Isotopes; D011506:Proteins; D012333:RNA, Messenger; D010649:Phenylalanine; D012313:RNA; D002701:Chloramphenicol; D007930:Leucine
CARBON ISOTOPES; CHLORAMPHENICOL; EXPERIMENTAL LAB STUDY; LEUCINE; PHARMACOLOGY; PHENYLALANINE; PROTEIN METABOLISM; RABBITS; RETICULOCYTES; RIBOSOMES; RNA; RNA, MESSENGER