Cytokinetic study on the effects of N⁴‐behenoyl‐1‐β‐d‐arabinofuranosylcytosine on murine leukemic cells L 1210: A comparison with the effects of 1‐β‐d‐arabinofuranosylcytosine

Abstract

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.

A Maximum Common Subgraph Kernel Method for Predicting the Chromosome Aberration Test

“…70 The connectivities with positive contribution to classification in Figures 7c and 8 include part of the cytosine moieties. Both enocitabine 71 and cytarabine 72 (Figures 7c and 8, respectively) act as antimetabolites inducing the premature termination of growing DNA chains. In addition, they inhibit several enzymes involved in the synthesis of DNA precursors, such as DNA polymerases and nucleotide reductase enzymes, leading to impairment of DNA synthesis.…”