Abstract

The effect of Adriamycin (ADR) and irradiation on the ultimate fate of Chinese hamster ovary cells treated in G 2, phase was investigated utilizing the mitotic selection procedure for cell cycle analysis coupled with a plating efficiency assay. As cells were selected in mitosis, they were inoculated at appropriate numbers and incubated for analysis of colony-forming ability. The parameters obtained, expressed as a function of time after initiation of treatment, were the number of mitotic cells selected per shake (the mitotic yield), the plating efficiency (surviving fraction), and the number of surviving cells per shake (the product of the first two parameters). Cells treated with a 20 min pulse of 1.0 μ/ml ADR exhibited a transient division delay with a decrease in plating efficiency at the nadir of the mitotic yield curve. Cells treated with 150 rad of X-ray displayed a similar response except that surviving fraction decreased immediately after treatment. As cells recovered from the radiation-induced division delay, the surviving fraction increased to a plateau level close to that of the control. When cells were treated with both ADR and X-ray, the result was an increase in the duration of the division delay, a decreased surviving fraction, and consequently, a decreased number of surviving cells per shake. These results suggest the possibility of predicting optimum schedules for sequential treatment with these two agents based on a knowledge of the perturbatory effects on cell cycle progression for those cells most likely to retain clonogenic ability.

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