5-FLUOROCYTOSINE - INHIBITION OF HEMATOPOIESIS INVITRO AND REVERSAL OF INHIBITION BY URACIL

The in vitro effect of 5-fluorocytosine on human and murine hematopoiesis was studied by means of soft-gel assays for erythroid and myeloid colony-forming cells. The drug consistently inhibited colony formation by granulocyte-monocyte and erythroid precursor cells. Clear effects were observable at concentrations of 5-fluorocyto-sine of 5 X 10-5 M (6.5 μg/ml), and concentrations of 5 X 10-4 M (65 μg/ml) caused -90% inhibition of cloning of bone marrow myeloid colony-forming cells from mice and normal humans. Greater concentrations of 5-fluorocytosine were required to inhibit erythroid progenitors than to inhibit myeloid precursors. Uracil competitively reversed the toxicity of 5-fluorocytosine. Our data strongly suggest that the hematopoietic toxicity of 5-fluorocytosine is mediated through cellular metabolism of the drug. The reversal of mammalian, but not of fungal, cytotoxic effects of 5-fluorocytosine by uracil may have important clinical applications. © 1979 by The University of Chicago.