title: Effects of the tricyclic nucleoside 6-amino-4-methyl-8-(beta-D-ribofuranosyl)- pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine on the viability and cell cycle distribution of L1210 cells in vitro.
abstract: TCN (1 microM) totally inhibited the growth of L1210 cells in culture and caused progressive loss of cellular viability, as indicated by a decreased clonogenicity and nigrosin dye exclusion. After 24 h or more of TCN treatment, a significant fraction of the cells had shrunk in size but did not fragment into dye-impermeable vesicles as reported previously for N1S1-67 hepatoma cells (P. G. W. Plagemann, J. Natl. Cancer Inst., 57: 1283-1295, 1976). TCN-induced growth inhibition was accompanied by a block of cell cycle progression in G1 or at the G1-S boundary. At all TCN concentrations studied, progression of cells out from behind this block was evident as a depletion of the early S-phase population in comparison to controls, while increasing the concentration of TCN (0.1 to 1 microM) led to a progressive retention of cells in S phase, suggesting a slowing of progression through S phase. The fraction of S-phase cells incorporating [methyl-3H]thymidine and the amount of [methyl-3H]thymidine incorporated per labeled cell were both decreased by TCN treatment. Increasing the concentration of TCN (0.1 to 1 microM) progressively decreased DNA synthesis and increased cell lethality. Thus it appeared that inhibition of DNA synthesis might cause the retention of cells in S phase which is associated with TCN lethality.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000032:analysis; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008940:Mitotic Index / Q000187:drug effects; D012263:Ribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012263:Ribonucleosides; C023764:triciribine