The inhibition of protein synthesis and respiration in mouse ascites tumor cells by chloramphenicol and its isomers and analogues.

Abstract

D(−)-threo-Chloramphenicol has been found to inhibit protein synthesis, respiration, and RNA synthesis in mouse ascites cells. These inhibitions are prevented by glucose. Chloramphenicol gives 50% inhibition of respiration and protein synthesis at between 1.4 and 1.6 mM and between 1.1 and 1.4 mM, respectively. In the presence of increasing amounts of chloramphenicol there is also a progressive drop in the level of ATP. Isomers and analogues of chloramphenicol inhibit both protein synthesis and respiration. The inhibitory strength decreases as follows: methylthio analogue, chloramphenicol, L(+)-threo-isomer, L-erythro-isomer, chloramphenicol base, methylsulfonyl analogue, and sulfamoyl analogue. The D(−)-threo- and L(+)-threo-isomers are taken up equally by the cells to a concentration of 1.1 to 1.4 times that of the medium. It is concluded that the inhibition of protein synthesis in ascites cells by chloramphenicol is not a direct effect but is due to the inhibition of respiration and ATP production, which in turn depends on the inhibition of NADH oxidation by the antibiotic. Rotenone has also been found to inhibit protein synthesis.