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 L 1210-CELLS INVITRO

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (12) , 6355-6361
Abstract
TCN (1 .mu.M) totally inhibited the growht 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 .mu.M) 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 cells were both decreased by TCN treatment. Increasing the concentration of TCN 10.1 to 1 .mu.M) 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.