Effects of cytosine arabinoside and daunorubicin on survival and cell cycle progression of chinese hamster ovary cells

Abstract. Kinetic and cytotoxic effects of cytosine arabinoside (Ara‐C) and daunorubicin (DNR) on exponentially growing Chinese hamster ovary (CHO) cells were measured by flow cytometry and by a colony‐forming assay, respectively. With Ara‐C alone, increasing drug concentrations between 10^‐7 M, for up to 27 hr, were associated with increased inhibition of cell progression through the S phase. Even at the very toxic concentration of 10^‐4 M, however, cells were able to enter and progress slowly through S. DNR, which appears to enter these cells relatively slowly, was highly toxic even at 2 times 10^‐7 M. It decreased the rate of progression through S phase and caused cells to accumulate in G₂, except at the highest concentration (2 times 10^‐5 M), at which progression was inhibited throughout the cycle. Simultaneous exposure of the cells to Ara‐C and DNR yielded cell cycle distributions similar to those of the former drug alone. When cells were exposed to a non‐lethal dose of Ara‐C and to a dose of DNR which was lethal to a fraction of the cell population (or conversely), either simultaneously or separated by a drug‐free interval, small, but in some cases significant, drug interactions were observed. These effects were not caused by druginduced redistribution of cells within the cell cycle, but may have been related to the effects of the non‐lethal drug on DNA synthesis rate.