Differential In-vitro Toxicity of Chloramphenicoi, Nitroso-chloramphenicol, and Thiamphenicol

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Abstract
The comparative effects of chloramphenicol, its nitroso derivative, and thiamphenicol on a number of metabolic parameters in vitro, including DNA and mitochondrial protein synthesis, and the effects of these agents on isolated double-stranded DNA are described. Evidence is presented in support of the hypothesis that the p-nitro group of chloramphenicol is the structural feature underlying aplastic anemia caused by this drug. The capacity of small concentrations of nitroso-chloramphenicol and large concentrations of chloramphenicol to produce breaks in double-stranded DNA suggests that, in the predisposed host, either chloramphenicol or its nitroso derivative may cause DNA damage and mutation, ultimately leading to aplastic anemia and/or leukemia.

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