Abstract
Mouse myeloid leukemia cells (M1) were induced to different-iate in vitro by treatment with dexamethasone. The incorporation of [3H] thymidine into acid-insoluble materials began to decline after 10 h treatment. This reflected the differentiation-associated decline of DNA synthesis activity, since (i) the thymidine was almost exclusively incorporated into nuclear DNA, (ii) the incorporation was completely blocked by arabinofuranosylcytosine and (iii) the differentiation-associated changes of intracellular pool size and specific activity of thymidine were negligible. Cell fractionation by discontinuous Ficoll-Urografin density gradients revealed that the DNA synthesis of the differentiat-ed cells declined with the decreased density, or ratio of nucleus size to cell size (N/C ratio). Autoradiographic analysis showed that the decrease in DNA synthesis activity was due to the accumulation of "unlabeled" cells, which exhibited a much lower N/C ratio than "labeled" cells. Dexamethasone treat-ment also caused specific reduction in the proportion of S phase cells. These results indicate that M1 cell differentiation is closely coupled with the cessation of DNA synthesis.
