Molecular basis of chloramphenicol and thiamphenicol toxicity to DNA in vitro

The action of thiamphenicol and reduced chloramphenicol on DNA has been investigated in vitro. Reduced chloramphenicol causes DNA damage which is dependent upon reduction of the nitro group and which is characterized by helix destabilization and strand breakage. Although the reduction process requires six electrons indicating formation of the amine in 100% yield the toxic agent is most probably a short-lived reduction intermediate. We propose the one-electron nitro radical anion rather than the nitroso derivative as the toxic agent responsible for DNA damage related to aplastic anaemia. In contrast, thiamphenicol produces no such effects on DNA.