Synchronization of L1210 leukemia with XXXX infusion and the effect of subsequent pulse dose chemotherapy.

@entity632 @entity5 @entity19 @entity1862 @entity665 @entity2592 @entity1500 @entity1499
Studies were performed to synchronize L1210 @entity5 cells in S phase in an effort to maximize the effect of subsequent pulse dose chemotherapy. @entity1862 (HU) was administered by continuous iv infusion 5 days after @entity5 implantation. Perturbation effects on the S-phase cells were measured by serial @entity665 labeling indices. Effects on cell-cycle progression were measured by DNA content distribution analysis using flow cytometry. Synchronization of @entity5 cells was achieved with HU infusion (48 mg/kg/hour x 24 hours), resulting in 90% of the cells in S phase. Following infusion, synchronous progression of S-phase cells into G2/M and then G1 was apparent from +0 to +10 hours later. The susceptibility of HU-synchronized cells to subsequent chemotherapy was determined by treating @entity19 with @entity2592 ( @entity2592 ), @entity1499 ( @entity1500 ), or @entity632 (ADR) pulse doses at various intervals following infusion. Synergy, measured by prolongation of survival times, resulted when @entity2592 was administered immediately after the end of the infusion. Survival times then decreased as the fraction of cells in S phase decreased. In contrast, the survival times of @entity19 treated with @entity1500 or ADR pulse doses after HU infusion were additive at best and did not correlate with fluctuations in the S phase compartment. Therefore, prior synchronization of @entity5 cells in S phase was therapeutically advantageous when coupled with appropriately timed @entity2592 pulse doses. There was little advantage in combining HU infusion with subsequent @entity1500 or ADR therapy.
