Koeffler H P, Golde D W
J Infect Dis. 1979 Apr;139(4):438-43. doi: 10.1093/infdis/139.4.438.
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 x 10(-5) M (6.5 micrograms/ml), and concentrations of 5 x 10(-4) M (65 micrograms/ml) caused approximately 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 5-5-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.
通过针对红系和髓系集落形成细胞的软琼脂试验，研究了5-氟胞嘧啶对人和小鼠造血作用的体外效应。该药物持续抑制粒细胞-单核细胞和红系前体细胞的集落形成。在5-氟胞嘧啶浓度为5×10⁻⁵ M（6.5微克/毫升）时可观察到明显效应，而5×10⁻⁴ M（65微克/毫升）的浓度可使来自小鼠和正常人的骨髓髓系集落形成细胞的克隆受到约90%的抑制。抑制红系祖细胞所需的5-氟胞嘧啶浓度高于抑制髓系前体细胞所需的浓度。尿嘧啶可竞争性逆转5-氟胞嘧啶的毒性。我们的数据有力地表明，5-氟胞嘧啶的造血毒性是通过该药物的细胞代谢介导的。尿嘧啶对5-氟胞嘧啶的哺乳动物细胞毒性作用而非真菌细胞毒性作用的逆转可能具有重要的临床应用价值。
