Abstract

3'-Deoxy-3'-fluorothymidine (FT), at a concentration of 30 muM, is capable of inducing about 50% of human myeloid K562 cells to differentiate while reducing the growth potential (clonogenicity, growth rate) approximately by one half. For comparison, arabinosylcytosine (Ara C), at 0.1 muM, causes the same percentage of differentiation, but cell proliferation is abolished by >80%. Induction of differentiation is more correlated with the inducer concentration than with incubation periods for both agents. After removal of FT after 5 days of treatment, the cells resume normal growth for the next 5 days. The absolute number of differentiated cells increases within this period. In accordance with their effect on the growth potential, the shift of the colony/cluster ratio towards higher numbers of clusters is greater for Ara C than for FT. Cells treated with either compound are larger than control cells. While in control colonies only very few differentiated cells are found by microscopic inspection, up to 50% of FT treated colony cells are estimated as differentiated. In many clusters and small colonies of Ara C treated cells more than 80% of the cells are benzidine-positive. Loss of clonogenicity of CFU-GM from mouse bone marrow is stronger with Ara C treatment in liquid cell culture for 2 days than with FT treatment in the same concentration range.

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