Cytokinetic study on the effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine on murine leukemic cells L 1210: a comparison with the effects of 1-beta-D-arabinofuranosylcytosine.
The effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) on the cell cycle of murine leukemic cells (L 1210 cells) were compared with those of 1-beta-D-arabinofuranosylcytosine (ara-C), known to be effective for acute leukemia. In a cytokinetic study, a combination of Feulgen microcytofluorometry and tritiated thymidine autoradiography (3H-TdR ARG) was used to measure DNA content and to determine DNA synthesis simultaneously in a single cell. Administration of 200 mg/kg of BH-AC significantly prolonged the survival time of mice bearing L 1210. In addition, the cells in the G1 + S1 phases increased with time, accounting for 94.4 per cent of all cells measured at 48 h after the administration, compared to 73.7 per cent before administration. On the other hand, following the administration of 86 mg/kg of ara-C (equivalent to 200 mg/kg of BH-AC), the percentage of cells in the S1 + S2 phases increased maximally to 75.9 per cent at 18 h. Cytokinetic studies further showed that BH-AC administration blocks DNA synthesis of the cells in the S-phase for a longer period than does ara-C. These results suggest that the prolonged inhibition by BH-AC on DNA synthesis allows cells to accumulate in the S-phase to a greater degree.
Maruo
N
N
Horiuchi
H
H
Nakabo
T
T
Kondo
M
M
Nakamura
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D004396:Coloring Agents; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D007399:Interphase / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D012394:Rosaniline Dyes; D013194:Staining and Labeling; D013997:Time Factors
D000970:Antineoplastic Agents; D004396:Coloring Agents; D004273:DNA, Neoplasm; C007722:Feulgen stain; D012394:Rosaniline Dyes; D003561:Cytarabine; C015019:enocitabine