Cell kinetic studies of the cytostatic and cytocidal effect of 1-beta-D-arabinofuranosylcytosine on the L1210 ascites tumor.
The effect of 1-beta-D-arabinofuranosylcytosine (ara-C) on mouse L1210 ascites tumor cells was studied in vivo with cell kinetic methods. Injection of ara-C (200 mg/kg) leads to an immediate inhibition of DNA synthesis and, thus, to a block of G1 cells at the G1-S border. This dose of ara-C kills a considerable fraction (at least 54%) of the L1210 cells. A double-labeling experiment with [3H]thymidine and [14C]thymidine which permits the distinction of cells in different cycle phases shows that ara-C kills the majority of cells in S phase, while only a minor fraction of G1 cells are lethally damaged. A multicompartment model is utilized to derive from the results of the double-labeling experiment the rates of cell loss out of the different cycle phases. Eighty-seven percent of the cells that are in S phase at the time of ara-C application and 21% of the cells in G1 are killed by ara-C. The repopulation of the tumor starts from the remaining G1 cells. A mean life span of the necrotic cells of 1.9 hr is derived from the model.
D000818:Animals; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology / Q000503:physiopathology*; D008433:Mathematics; D051379:Mice; D008815:Mice, Inbred Strains; D014316:Tritium
D002250:Carbon Radioisotopes; D003561:Cytarabine; D014316:Tritium