DIFFERENTIAL-EFFECTS OF CYTO-TOXIC AGENTS ON HEMATOPOIETIC PROGENITORS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2338-2342
Abstract
To predict the effect of chemotherapeutic agents on the hematopoietic progenitor compartment, it is necessary to have a hypothesis concerning the dynamics of the cells within the compartment. By viewing this compartment as a continuum of cells with varying self-renewal capacity, the significance of the stem cell damage incurred following a single drug dose can be assessed. Vinblastine, 5-fluorouracil, cyclophosphamide, busulfan, and 1,3-bis(2-chloroethyl)- 1-nitrosourea (BCNU) [all antitumor agents] were investigated. The acute toxicity of the drug-exposed marrow [mouse] was studied by the colony-forming units-spleen (CFU-S) and agar diffusion chamber assay. Busulfan and BCNU killed CFU-S preferentially. By following CFU-S recovery for 14 days post-drug, different recovery patterns are noted. Busulfan and BCNU produce prolonged depression in CFU-S; cyclophosphamide and 5-fluorouracil show relatively rapid recovery. If the Rs [ratio of CFU-S] (a measure of proliferative capacity) after drug is determined, busulfan and, to a lesser extent, BCNU produce a prolonged depression without return to normal even 650 days post-drug. No such depression is noted with the other drugs. The data from the recovery curves and Rs support the notion of stem cells being heterogeneous with regard to self-renewal capacity. The agar diffusion chamber and CFU-S acute survival curves would not have predicted which drugs cause significant proliferative damage. Only with the use of CFU-S recovery and ratio of CFU-S can prolonged marrow damage be ascertained.