EFFECT OF MYLERAN ON MURINE HEMATOPOIESIS .2. DIRECT AND HOST-MEDIATED ACTION ON PROLIFERATIVE CAPACITY AND DIFFERENTIATION BIAS OF SPLEEN COLONY-FORMING UNITS (CFU-S)

The direct and host‐mediated effects of the antileukemia agent Myleran (Busulphan, MY) on murine hemopoietic progenitor cells was assessed in vivo in the differential spleen colony system and in vitro in the agar gel granulocytic colony system. MY destroyed both spleen colony forming cells (CFU‐S) and agar gel colony forming cells (CFU‐C), the effect on CFU‐S being ten‐fold more severe than that on CFU‐C. Moreover, MY indirectly enhanced the seeding efficiency of CFU‐S and directly impaired their capacity to self‐replicate. MY also acted both directly and indirectly to impair the capacity of CFU‐S to generate granulocytic spleen colonies. Both the direct and indirect effect of MY on the CFU‐S' differential spleen colony forming bias was maintained following their retransplantation into lethally irradiated hosts that had not been exposed to MY. Finally, MY acted indirectly to impair the capacity of CFU‐S to differentiate to CFU‐C. the phenomenon appeared to be humorally mediated, since it was induced by exposure of CFU‐S to the MY‐treated host environment but not by their exposure to the MY‐damaged splenic stroma. an effect on the CFU‐S themselves does not appear to have been involved, since impairment of CFU‐C generation could be reversed by retransplantation of the CFU‐S into lethally irradiated hosts that had not been exposed to MY. the findings were compatible with the concept that MY (a) affects the membrane permeability of CFU‐S to modulating agents such as hemopoietins, and/or (b) selectively enhances survival of a subpopulation of erythrocytically committed CFU‐S, and/or (c) selectively abrogates survival of a subpopulation of cells capable of inhibiting commitment to the erythroid cell line. Copyright © 1978, Wiley Blackwell. All rights reserved