Effect of L-Asparaginase on Mouse Bone Marrow, Assayed by In Vitro Culture

L-asparaginase administered in therapeutic doses to mice was found to reduce the total number of nucleated marrow cells and colony-forming cells when assayed 4 hours after administration by a methylcellulose bone marrow culture technique. Both marrow cellularity and the fraction of surviving IVCFC/femur were normal by 24 hours after injection, except with very large doses, at a time when there were sufficient quantities of L-asparaginase free or cellularly bound within the marrow to be toxic to the culture system. The enzyme could be removed from the marrow specimens with repeated washings. It is postulated that the bone marrow of the mouse is similar to the regenerating rat liver in that both have the ability to compensate for Lasparagine depletion, even in the presence of active L-asparaginase. The rarity of clinically observed myelosuppression in human subjects could be the result of a similar mechanism.