Molecular Pharmacology, Vol 13, 504-511, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Deoxyribonucleic Acid Synthesis in Ehrlich Ascites Cells by Chloramphenicol

¹ Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada L8S 4J9
² Department of Biological Sciences, St. John’s University, New York, New York 11432

The effect of D(-)-threo-chloramphenicol and a number of its analogues on protein, RNA, and DNA biosynthesis in isolated Ehrlich-Lettré mouse ascites cells was examined. The methylsulfonyl analogue (thiamphenicol) and the sulfamoyl analogue (Tevenel) inhibited DNA synthesis slightly in both the presence and absence of glucose. The methylthio analogue inhibited all three processes; glucose reversed the inhibition at lower concentrations of the analogue, indicating that inhibition was secondary to the inhibition of NADH oxidation. Chloramphenicol also inhibited all three processes; the inhibition of protein and RNA synthesis was reversed by glucose, but the inhibition of DNA synthesis was slightly greater in the presence of glucose. The inhibition of DNA synthesis by chloramphenicol was similar under aerobic and anaerobic conditions and was not the result of an effect on the [³H]thymidine nucleotide pool. Inhibition required whole cells; it was slight with lysed cells, isolated nuclei, or purified DNA polymerases. The N-trifluoroacetyl analogue and the L(+)-threo isomer displayed patterns of inhibition of protein and DNA synthesis similar to that of chloramphenicol. The results are consistent with the possibility that chloramphenicol inhibits DNA synthesis in whole cells in the presence of glucose because the antibiotic undergoes metabolism, possibly reduction, in cells, and that a p-nitro group is important for this effect.

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