Thioguanine-induced S and G2 blocks and their significance to the mechanism of cytotoxicity.
Thioguanine-induced S and G2 blocks and their significance to the mechanism of cytotoxicity.
复制标题
硫鸟嘌呤诱导的 S 和 G2 阻滞及其对细胞毒性机制的意义。
作者：
L. Wotring;J. R. Roti Roti
用培养的L1210小鼠白血病细胞研究了6-硫鸟嘌呤（TG）的延迟细胞毒作用。使用流式细胞术分析，将连续处理10(-5)M TG的群体的细胞周期分布与对照细胞进行比较。tg处理的细胞在G2-M期占总细胞数的比例增加，G1期减少，S期保持恒定水平。然而，在TG处理期间，[甲基- 3h]胸腺嘧啶标记指数显著下降。因此，似乎有些细胞停留在S期，而G1细胞由于无法合成DNA而没有进入S期。为了检验G2和S细胞进展阻滞的重要性，将细胞暴露于10(-5)M TG致死处理12小时，然后返回正常培养基。在这些条件下，S和G1的群体比例都下降了，在加入TG 60小时后，G2中积累了近一半的细胞，而对照细胞的G2比例不到十分之一。这些结果表明，TG的延迟细胞毒性作用与添加TG后第二个G2期的细胞进展阻滞有关，而S期细胞的保留似乎是由于TG易于逆转的二次效应。
The delayed cytotoxic effect of 6-thioguanine (TG) was studied using L1210 mouse leukemic cells in culture. The cell cycle distribution of a population treated continuously with 10(-5) M TG was compared to that of control cells using flow cytometric analysis. The TG-treated cells had an increase in the fraction of the population in G2-M, a decrease in G1, and a constant level in S phase. However, the [methyl-3H]thymidine-labeling index decreased dramatically during TG treatment. Thus, it appeared that some cells were arrested in S phase and that G1 cells did not enter S phase, due to failure to synthesize DNA. To examine the importance of the G2 and S cell progression blocks, cells were exposed to a lethal treatment of 10(-5) M TG for 12 hr and returned to normal medium. Under these conditions, the fraction of the population in both S and G1 decreased, and nearly one-half of the cells accumulated in G2 by 60 hr after TG addition, compared to a G2 fraction of less than one-tenth for the control cells. These results showed that the delayed cytotoxic effect of TG was associated with a cell progression block in the second G2 phase after TG addition, whereas the retention of cells in S phase appeared to be due to readily reversible secondary effects of TG.