Partial synchronization of L1210 cells by 5-fluorouracil and its use in drug combinations

When L1210 cells growing logarithmically were exposed for 8 hr to a nonlethal dose of 5-fluorouracil (FU) (0.25 microgram/ml), the percentage of cells in S phase increased from 74.9% in the asynchronous culture to 93% in the FU-treated culture. This resulted in increased cell-kill by S-phase-specific inhibitors [1-beta-D-arabinofuranosylcytosine (ara-C), 5-hydroxy-2-formylpyridinethiosemicarbazone] when they were added to a culture partially synchronized by pretreatment with FU. For example, 2 hr exposure to ara-C alone or ara-C plus FU (added simultaneously to asynchronous culture) gave 28.8 and 25.8% survival, respectively, compared to 6.8% survival when ara-C was added for 2 hr to the partially synchronized culture. Eight to 12 hr after FU removal, the culture became asynchronous, such that ara-C addition at this time did not result in increased cell-kill. Cultures pretreated with FU were also highly sensitive to vincristine and Adriamycin. Adriamycin acted synergistically with FU (after 8 hr pretreatment) in killing L1210 cells.