Wotring L L, Roti Roti J L
Cancer Res. 1980 May;40(5):1458-62.
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.
利用培养的L1210小鼠白血病细胞研究了6-硫鸟嘌呤（TG）的延迟细胞毒性作用。使用流式细胞术分析，将连续用10⁻⁵ M TG处理的细胞群体的细胞周期分布与对照细胞进行比较。经TG处理的细胞中，处于G2-M期的细胞群体比例增加，G1期减少，S期保持恒定水平。然而，在TG处理期间，[甲基-³H]胸苷标记指数急剧下降。因此，似乎一些细胞停滞在S期，并且G1期细胞由于无法合成DNA而未进入S期。为了研究G2期和S期细胞进展阻滞的重要性，将细胞暴露于10⁻⁵ M TG的致死处理12小时，然后放回正常培养基中。在这些条件下，S期和G1期的细胞群体比例均下降，与对照细胞中G2期比例不到十分之一相比，添加TG后60小时，近一半的细胞积累在G2期。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，而细胞滞留在S期似乎是由于TG易于逆转的次要作用。
