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.
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.
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发表时间：
1985-12
期刊：
影响因子：
11.2
通讯作者：
L. Wotring;J. E. Passiatore;Joseph L. Roti Roti-Joseph-L.-Roti-Roti-2246339882;Jerry L. Hudson;Leroy B. Townsend
中科院分区：
文献类型：
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作者：
L. Wotring;J. E. Passiatore;Joseph L. Roti Roti-Joseph-L.-Roti-Roti-2246339882;Jerry L. Hudson;Leroy B. Townsend
TCN (1 microM) 完全抑制培养物中 L1210 细胞的生长，并导致细胞活力逐渐丧失，如克隆形成性降低和苯胺黑染料排除所示。 TCN 处理 24 小时或更长时间后，很大一部分细胞尺寸缩小，但没有碎裂成染料不可渗透的囊泡，如先前报道的 N1S1-67 肝癌细胞（P. G. W. Plagemann, J. Natl. Cancer Inst., 57: 1283-1295, 1976）。 TCN 诱导的生长抑制伴随着 G1 期或 G1-S 边界细胞周期进展的阻滞。在研究的所有 TCN 浓度下，与对照相比，细胞从该块后面的进展明显，因为早期 S 期群体的消耗，而增加 TCN 浓度（0.1 至 1 µM）导致细胞逐渐保留在 S 期，表明 S 期进展减慢。通过TCN处理，掺入[甲基-3H]胸苷的S期细胞分数和掺入每个标记细胞的[甲基-3H]胸苷的量均减少。增加 TCN 浓度（0.1 至 1 µM）会逐渐降低 DNA 合成并增加细胞致死率。因此，抑制 DNA 合成可能会导致细胞停留在 S 期，这与 TCN 致死性相关。
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.