EVIDENCE FOR EARLY RECRUITMENT OF GRANULOCYTE PRECURSORS DURING HIGH-DOSE METHOTREXATE INFUSIONS IN MICE

  • 1 January 1976
    • journal article
    • research article
    • Vol. 48  (2) , 301-307
Abstract
The effects of constant exposure to high concentrations of methotrexate [an antineoplastic agent] in vivo on the committed stem cell (CFU-C) were studied by in vitro culture of mouse bone marrow. Bone marrow samples were obtained from animals receiving a continuous infusion and were cultured in a methotrexate-free semisolid gel system. The effects of methotrexate infusion on the pluripotent stem cell population (CFU-S) were studied as well. Constant exposure to 10-5 M methotrexate produced a rapid decrease in total nucleated cells/femur, reaching 35% of control at 12 h and remaining at approximately this level throughout 48 h of drug infusion. A decrease in the number of both CFU-C and CFU-S per femur was observed, which paralleled the drop in nucleated cells during the 1st 24 h. In contrast to an additional drop in the number of CFU-S, an increase of CFU-C number per femur was observed from 24-48 h. These data indicated a self-limited cell kill of nucleated bone marrow cells and suggested recruitment of CFU-C from the CFU-S pool between 24 and 48 h of infusion despite continued methotrexate infusion.