In vivo cell cycle phase-preferential killing of murine fibrosarcoma cells by cisplatin

Fibrosarcoma cells were separated by centrifugal elutriation. Selected populations enriched in G1-, S-, or G2 + M-phase cells were then injected (10(4) cells) into the tail veins of C3Hf/Kam mice. Twenty minutes after, 4 mg/kg of cisplatin was injected iv into one half of the animals in each experimental group. Fourteen days later the number of lung colonies was scored, and the surviving fractions were plotted against the elutriator fraction numbers. The results indicated that all phases of the cell cycle were sensitive to cisplatin but that the G1 phase was the most sensitive by a factor of ten. Biphasic dose-response curves were observed for unseparated control, S-phase, and G2 + M-phase tumor cell populations, indicating a resistant cell population. G1 cells, however, had long killing over four decades without the resistant tail. Using this in vivo system, it is concluded that cisplatin kills cells throughout the cell cycle but exhibits preferential killing of G1 tumor cells.