CELL KINETIC-STUDIES AFTER HIGH-DOSE ARA-C AND ADRIAMYCIN TREATMENT IN A SLOWLY GROWING-RAT LEUKEMIA MODEL (BNML) FOR HUMAN ACUTE MYELOCYTIC-LEUKEMIA

The effect of high-dose cytosine arabinoside (Ara-C; 1-.beta.-D-arabinofuranosyl cytosine) injections (200 mg/kg i.v.) on cell cycle perturbation was investigated in a slowly growing rat leukemia (BNML) which is a realistic model for human acute myelocytic leukemia. Flow cytometric analysis showed an initial decrease of cells in S phase from 26 to 13% and a subsequent accumulation of up to 50% at 10-14 h after injection. The low number of S phase cells during the first 8 h might be due to a combination of cell kill in S phase and a block at the G/S boundary. The origin of the accumulated S phase cells is probably the resting compartment; these recruited cells probably enter the proliferation phase as a synchronized cell population. By repeating the Ara-C injection at the time of accumulation of cells in S phase, a similar synchronized wave of recruited cells to that after the 1st Ara-C injection was observed. Flow cytometric analysis after adriamycin (7.7 mg/kg i.v.) treatment, which had been shown to be cytotoxic for BNML cells, showed no changes in cell cycle distribution. Apparently, adriamycin might have the same toxicity for cells in all of the different cell cycle phases.