Abstract

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-fluorocytosine of 5 × 10−5m (6.5 µg/ml), and concentrations of 5 × 10−4m (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-ftuorocytosine by uracil may have important clinical applications.

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