Schedule-dependent synergism of combinations of XXXX with @entity632 and @entity9864 with @entity632 .

@entity632 @entity19 @entity1862 @entity2592 @entity9864 @entity734
The lethal effects of combinations of @entity632 (ADR) and either @entity1862 (HU) or @entity9864 ( @entity2592 ) were studied in relation to drug-scheduling interval in @entity19 cells grown in vitro. @entity734 was determined by cell cloning in soft agar. Serial kinetic changes induced by a priming dose of HU or @entity2592 were monitored by flow cytometry and related to schedule-dependent cell killing by ADR. All drug exposures were for 1 hr. When ADR was given together with either HU or @entity2592 , cell log kill was additive. However, when ADR was given after exposure to either HU or @entity2592 , cell killing was increased up to 200- to 500-fold, respectively. Maximum schedule-dependent synergism was observed at a drug-scheduling interval of 2 hr; schedule-dependent synergism decreased as the interval between drugs was increased beyond 2 hr. Schedule-dependent synergism was not observed when the same drug combinations were given in reversed order. Drug-induced changes in the DNA histogram were not seen until 5 hr after HU exposure and 8 hr after @entity2592 exposure. Thus, the schedule-dependent synergism between ADR and either HU or @entity2592 cannot be explained by cell cycle blockade with synchronization of cells in S phase.
