INDUCTION OF DIFFERENTIATION OF HUMAN MYELOID LEUKEMIC K562 CELLS BY 3'-DEOXY-3'-FLUOROTHYMIDINE (COMPARISON WITH ARABINOSYLCYTOSINE)

3'-Deoxy-3'-fluorothymidine (FT), at a concentration of 30 muM, is cap able of inducing about 50% of human myeloid K562 cells to differentiat e while reducing the growth potential (clonogenicity, growth rate) app roximately by one half. For comparison, arabinosylcytosine (Ara C), at 0.1 muM, causes the same percentage of differentiation, but cell prol iferation is abolished by >80%. Induction of differentiation is more c orrelated with the inducer concentration than with incubation periods for both agents. After removal of FT after 5 days of treatment, the ce lls resume normal growth for the next 5 days. The absolute number of d ifferentiated cells increases within this period. In accordance with t heir effect on the growth potential, the shift of the colony/cluster r atio 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 e stimated as differentiated. In many clusters and small colonies of Ara C treated cells more than 80% of the cells are benzidine-positive. Lo ss 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 treatme nt in the same concentration range.