Differential in-vitro toxicity of chloramphenicol, nitroso-chloramphenicol, and thiamphenicol.
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.
D002453:Cell Cycle / Q000187:drug effects; D002701:Chloramphenicol / Q000031:analogs & derivatives / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D014176:Protein Biosynthesis; D013329:Structure-Activity Relationship; D013839:Thiamphenicol / Q000633:toxicity*
D002701:Chloramphenicol; C026099:nitrosochloramphenicol; D004247:DNA; D013839:Thiamphenicol