The effect of disulfiram on cyclophosphamide-mediated myeloid toxicity.

We have previously shown that disulfiram (DSF) blocks the urotoxicity of cyclophosphamide (CYT) in mice and increases the oncolytic effect of CYT in the L1210 murine leukemia. However, mice treated with CYT and DSF appeared to have longer-lasting neutropenia than animals treated with CYT alone. To determine whether DSF uroprotection of CYT-treated mice was associated with increased myeloid toxicity, we examined the effects of DSF plus CYT treatment on the bone marrow granulocyte/macrophage progenitor cell (GM-CFC). Marrow cellularity and GM-CFC numbers were analyzed at 1, 2 and 3 days after injection of CYT (62.5 or 125 mg/kg) or CYT plus DSF (200 mg/kg). CYT alone caused a decrease in total marrow cellularity varying from 20% to 50% of control. Animals given CYT plus DSF had a somewhat greater decrease in total marrow cellularity than those treated with CYT alone. However, in mice treated with CYT plus DSF, the GM-CFC were relatively well preserved and the recovery of the GM-CFC was not prolonged by DSF. It appears from these studies that the acute toxic effect of CYT on the granulocyte/macrophage progenitor cells is not enhanced by DSF.