KINETICS OF CYTOTOXICITY OF VM-26 AND VP-16-213 ON L1210 LEUKEMIA AND HEMATOPOIETIC STEM-CELLS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (9) , 1313-1320
Abstract
The in vivo effects of VM-26 and VP-16-213 [podophyllotoxin derivatives] on hematopoietic stem cells and [mouse] L1210 leukemia cells were quantitated using the spleen-colony assay technique. The effect of VM-26 on leukemia cells was further quantitated using an endpoint dilution assay. The dose-response curves for leukemic clonogenic cells for both agents when given by i.v. injection into mice were exponential and biphasic, indicating the existence of 2 populations. The survival of leukemia cells when VM-26 was administered as a 24 h infusion was less than that found for equivalent doses administered as single injections. The survival kinetics with respect to time for a low dose (0.02 mg/mouse) and a high dose (0.15 mg/mouse) of VM-26 were similar in that the decrease in survival was rapid, reaching a maximum effect within 4 h after administration. With the low dose, repopulation of the femoral marrow started immediately, whereas with the high dose, there was a 20 h delay in repopulation. The data from the increase in lifespan studies were in excellent agreement with the quantitative assays. The dose-response curves for the normal hematopoietic clonogenic cells were also exponential, but these cells were much less sensitive to the agents than were the leukemia cells.