DNA damage induced by chloramphenicol and its nitroso derivative: damage in intact cells.

We have postulated that the p-NO2 group of chloramphenicol (CAP) is the structural feature underlying aplastic anemia from this drug. In a series of studies to examine this hypothesis we have demonstrated the toxic nature of the CAP-reduction intermediate nitroso CAP (NO-CAP) and its damaging effect on isolated DNA in vitro. The present study was designed to examine the comparative effects of CAP, NO-CAP, and thiamphenicol (TAP) on the integrity of DNA in intact cells. By using the alkaline elution technique of Kohn, DNA damage in the form of single strand breaks could be readily demonstrated in cultured Raji cells and in PHA-stimulated normal human lymphocytes by small concentrations of NO-CAP (0.05-0.1 mM). A small but reproducible effect was observed from large concentrations of CAP (2 mM). In contrast, TAP, lacking the p-NO2 group, was without effect.