THE COMPARATIVE EFFECT OF BUSULPHAN ('MYLERAN') AND AMINOCHLORAMBUCIL ON HAEMOPOIETIC COLONY FORMING UNITS IN THE RAT

Using the spleen colony assay technique, it has been shown that busulphan (‘Myleran’) in a dose of 10^-2 g/kg (1/2 LD₅₀), causes a marked and prolonged depression (over 90%) in the number of colony forming units per femur (CFU/femur). This depression is apparent before there is any marked reduction of the total cell count per femur and is maximal 2–4 days after an intraperitoneal (i.p.) injection of the drug. It is then followed by a steady recovery, normal values being reached after about 20 days. In contrast, aminochlorambucil (2·5 x 10^-3) g/kg = 1/2 LD⁵⁰) although producing a rapid fall in the marrow cellularity has no discernable effect on the CFU/femur. If, however, a depression of CFUs is first induced by busulphan and, after allowing time for 50% recovery (13 days), aminochlorambucil is now given, a further severe depression of the CFUs/femur occurs resulting in a considerable prolongation of the neutropenia observed in the blood. The possible implications of this in the mode of action of these two drugs, and in the chemotherapy of leukaemia, are discussed.