The effects of D- and L-threo-chloramphenicol on the early development of the chick embryo.

I N many bacterial systems chloramphenicol has been shown to inhibit protein synthesis (Hahn & Wisseman, 1951; Gale & Folkes, 1953). The precise mechanism of this inhibition is not clear, although the evidence suggests that the interaction of the soluble RNA-amino acid complex with the ribosomes is prevented because the attachment of the messenger RNA to the ribosomes is itself impaired (Lacks & Gros, 1959; Nathans & Lipman, 1961; Jardetsky & Julian, 1964; Julian & Jardetsky, 1964). In contrast to its effect on bacterial systems, chloramphenicol has been reported to have little or no action on the protein synthesis by cell-free extracts of mammalian cells (Rendi, 1959; Ehrenstein & Lipmann, 1961). A basis for this resistance has been proposed by Vazquez (1964), who finds that whereas bacterial ribosomes bind chloramphenicol, ribosomes from other organisms do not. Nevertheless, it cannot be stated with any confidence that chloramphenicol has no effect on the protein synthesis of animal cells. It is known, for instance, that chloramphenicol causes chick embryos to develop abnormally (Blackwood, 1962), and in planarians it appears to alter the gradient of protein synthesis, as evidenced by its effect on the uptake of labelled amino acids (Flickinger, 1959). However, some caution is necessary in attributing all the biological effects of chloramphenicol to impaired protein synthesis, because apart from causing an arrest of protein synthesis, chloramphenicol can also prevent the uptake of certain ions by plant cells (Sutcliffe, 1960), an effect which may be related to the uncoupling of oxidative phosphorylation by the compound (Hanson & Hodges, 1963; Hanson, Stoner & Hodges, 1964). Fortunately the existence of isomers of chloramphenicol makes it possible, in some cases, to attribute the biological