Kinetic and cytotoxic effects of cytarabine and daunorubicin on cells in culture.

Overview

To investigate the possibility that a significant kinetic basis exists for the improved clinical response often obtained using drug combinations, Chinese hamster ovary cells were exposed to cytarabine and daunorubicin in combination. Cell survival was determined by a colony-counting assay; kinetic perturbations were monitored by flow cytometry. No major synergistic effects of the conditions, each drug appeared to provide some protection against the lethal effects of the other. By pairing a moderately toxic concentration of one drug with a nontoxic concentration of the other, we observed sequence-dependent differences in survival. These differences could not be attributed simple to alteration of the cell cycle phase positions by the nontoxic drug, combined with phase-specific lethality of the toxic drug. It is likely, however, that daunorubicin provided partial protection from cytarabine-related cytotoxicity through its effect on the DNA synthesis rate.