Chloramphenicol and protein synthesis in mammalian cells

L. Zelkowitz, G. K. Arimura, A. A. Yunis

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Abstract

Chloramphenicol in a concentration of 10 μg per milliliter causes complete inhibition of protein synthesis in sensitive bacteria, while concentrations far exceeding 100 μg per milliliter are needed to exert a similar effect in mammalian cells. Recently, it has been reported that in a cell-free system from rabbit reticulocytes, protein synthesis was equally sensitive to chloramphenicol as in bacteria and that the drug exerted this effect by preventing the binding of mRNA to ribosomes. In order to examine this problem parallel studies were carried out in both mammalian cells (rabbit reticulocytes) and in sensitive E. coli. The following results were obtained. (1) Protein synthesis in reticulocytes, both in whole cells and cell-free systems, was indeed resistant to chloramphenicol. (2) The small inhibitory effect observed at therapeutic chloramphenicol levels was not related to the concentration of mRNA. (3) Chloramphenicol did not affect the binding of mRNA to reticulocyte ribosomes nor did it bind to the ribosomes itself. (4) The results obtained in bacteria were in complete agreement with previously reported data: chloramphenicol in small concentrations inhibited protein synthesis both in whole cells and in cell-free system. The drug became bound to bacterial ribosomes but did not prevent the binding of mRNA; these results are consistent with recently reported data showing that chloramphenicol inhibited protein synthesis in bacteria by interfering with peptide bond formation. It is concluded that the response of the protein synthesizing machinery of mammalian cells to chloramphenicol is different from that of bacteria.

Original languageEnglish (US)
Pages (from-to)596-609
Number of pages14
JournalThe Journal of Laboratory and Clinical Medicine
Volume71
Issue number4
StatePublished - Apr 1 1968

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Zelkowitz, L., Arimura, G. K., & Yunis, A. A. (1968). Chloramphenicol and protein synthesis in mammalian cells. The Journal of Laboratory and Clinical Medicine, 71(4), 596-609.