THIOGUANINE-INDUCED S-BLOCK AND G2-BLOCK AND THEIR SIGNIFICANCE TO THE MECHANISM OF CYTO-TOXICITY

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (5) , 1458-1462
Abstract
The delayed cytotoxic effect of 6-thioguanine (TG) was studied using L-1210 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. The [methyl-3H]thymidine-labeling index decreased dramatically during TG treatment. 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 h and returned to normal medium. Under these conditions, the fraction of the population in S and G1 decreased; nearly 1/2 the cells accumulated in G2 by 60 h after TG addition, compared to a G2 fraction of less than 1/10 for the control cells. The delayed cytotoxic effect of TG was apparently associated with a cell progression block in the 2nd G2 phase after TG addition; the retention of cells in S phase appeared to be due to readily reversible secondary effects of TG.

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