Induction of Differentiation of U937 Leukemia Cell Line by a New Nucleoside Analogue, 1-Phenoxymethyl-6-Azauracil

Analogues of purines or pyrimidines have been reported to induce differentiation, to inhibit the growth of myeloid cells and to be useful in the treatment of leukemia. Objective: To investigate the effect of a new nucleoside analogue designated 1-phenoxymethyl-6-azauracil on the growth and differentiation of a monoblast-like human histiocytic lymphoma cell line, U937, capable of terminally differentiating in vitro to functionally mature monocytes. Methods: The synthesis of 1-phenoxymethyl-6-azauracil is described. Differentiation activity of this compound was measured by the assessment of morphologic maturity and the ability of U937 cell line to induce nitroblue tetrazolium (NBT) reduction. The results were compared with the same effect of retinoic acid (RA), a known inducer of differentiation. Results: U937 cell line was induced to differentiate into monocyte-like cells by incubation with 1 μM of 1-phenoxymethyl-6-azauracil. At this concentration, NBT reducing activity was observed in 39.3% of compound-treated cells in comparison with 48.3% of RA-treated cells. Treatment of U937 cell line with 1μM of 1-Phenoxymethyl-6-azauracil and the same concentration of RA increased the number of mature cells up to 43.5% and 68.5%, respectively. Increases in the number of mature cells and NBT positivity were correlated with the reduction in the cell number. Conclusion: The new synthesized compound is able to induce differentiation of U937 cell line.