Effect of three alkylating antimitotic agents and their metabolites on in vitro monogranulocytic colony forming cells from mouse bone marrow.

The effects of oxazaphosphorine cytostatics were studied on monogranulocytic colony forming cells from mouse bone marrow in methylcellulose culture. Cyclophosphamide, ifosfamide, trofosfamide and two secondary metabolites showed a weak activity (ED50 between 5 x 10(-4) mol/l and 5 x 10(-5) mol/l). On the contrary, a high toxicity was observed with phosphoramide mustard and especially hydroperoxycyclophosphamide (ED50: 2.5 x 10(-6) mol/l and 4 x 10(-7) mol/l). These results suggest that these metabolites are the carriers of cytotoxic specificity. The differentiation of the three types of colonies (granulocytic, monocytic and mixed) revealed no specific effect of the drugs for a given series. On the other hand, the staining of colonies revealed some mitotic abnormalities (agglutination bridge, micronuclei and cytodieretic alteration).