Effects of oxazaphosphorine cytostatics on granuloid progenitor cell (CFUc) proliferation in mice

The effects of oxazaphosphorine cytostatics were studied on granulocytic/monocytic colony forming cells from mice bone marrow in methylcellulose culture. Cyclophosphamide, ifosfamide, trofosfamide and two secondary metabolites show a weak activity in vitro (Inhibitory Dose--50% (ID50) between 5 X 10(-4) M and 5 X 10(-5) M). By contrast, a high cytostatic activity was observed with phosphoramide mustard and especially with hydroperoxycyclophosphamide (ID50: 2.5 X 10(-6) and 4 X 10(-7) M). These results suggest that these metabolites are active. The differentiation of the three types of colonies (granulocytic, monocytic and mixed) showed no specific effect of the drugs for a given series. After in vivo treatment, cyclophosphamide, ifosfamide and trofosfamide induce an important decrease of nucleated bone marrow cells. This decrease is maximum on the third day and regresses when the treatment is interrupted. On the first day of the culture an inhibition of the proliferation of granulocytic/monocytic progenitor cells is observed. An important statistically significant stimulation of these same progenitor cells is however noted later.