The myelotoxicity of chloramphenicol: in vitro and in vivo studies: I. In vitro effects on cells in culture

1 Chloramphenicol is used extensively in non-industria lized countries for the treatment of life-threatening infections because it is cheap and effective, despite its known hemotoxicity and linkage to fatal aplastic anaemia. It is important to define the mechanism of toxicity so that means can be devised to ameliorate the toxic effects in order to produce safer usage.

2 Chloramphenicol, at concentrations from 5 mM to 2 mM initiated apoptosis in dividing cells from a monkey kidney-derived cell line and in haematopoie tic progenitor cells from human neonatal cord blood.

3 Growth of progenitor cells was suppressed at concen trations of chloramphenicol which would be consid ered less than therapeutic during patient treatment.

4 These effects could be ameliorated in progenitor cells by co-culture with the antioxidant mercaptoethyla mine and in monkey kidney cells by co-culture with vitamin C.

5 This is the first report of apoptosis in chloramphenicol toxicity and suggests a possible link between a metabolic event i.e. the production of free radicals; a morphological effect, apoptosis; and a clinical effect, bone marrow suppression and aplastic anaemia.