Kinetics of the Lethal Effect of Actinomycin D on Normal and Leukemic Cells1

Spleen colony assays were used to quantitate the cytocidal effect of actinomycin D on leukemic cells and normal hematopoietic stem cells. Different doses of actinomycin D were administered to either normal or leukemia-bearing mice, and the surviving fraction of these cell populations was determined. Following single injections of the drug, the killing of both the normal and leukemic cell popula tions was found to occur over an extended period of time. The kinetics of killing of both cell populations was dose dependent with regard to both the final survival level and the time at which the minimum survival level was reached. The malignant cells exhibited a greater sensitivity than the normal cells. Both this difference in sensitivity and the ki netics of the lethal action of actinomycin D on both cell populations are discussed in terms of the difference in the proliferative states of the two cell populations and the known cellular effects of actinomycin D.