TRIMIDOX-MEDIATED MORPHOLOGICAL-CHANGES DURING ERYTHROID-DIFFERENTIATION IS ASSOCIATED WITH THE STIMULATION OF HEMOGLOBIN AND F-CELL PRODUCTION IN HUMAN K562 CELLS

Trimidox (3,4,5-trihdroxybenzamidoxime) has been shown to reduce the a ctivity of ribonucleotide reductase with accompanied growth inhibition and differentiation of mammalian cells. Hydroxyurea (HU) is the only ribonucleotide reductase inhibitor in clinical use for the treatment a nd management of sickle cell anemia, since this compound increases fet al hemoglobin (Hb F) production: a potent inhibitor of sickle hemoglob in (Hb SS) polymerization, However, the main limitations of HU is its lack of potency, myelosuppression and short half life. These studies i nvestigated the effects of trimidox on the induction of hemoglobin and F-cells production in K562 erythroleukemia cells. Our study reveals t hat trimidox exhibits concentration dependent inhibitory effect on K56 2 cells with increase in benzidine positive normoblasts and F-cells pr oduction as well as morphological changes typical of erythroid differe ntiation. These findings provide the first evidence that the growth in hibitory differentiation of cells induced by trimidox enhance hemoglob in and F-cells production. (C) 1998 Academic Press.