Benestad H B, Warhuus K, Reikvam A
Exp Hematol. 1977 Sep;5(5):408-14.
The lethal effect of hydroxyurea (HU) on normal and regenerating mouse bone marrow was examined in vivo and in vitro. Progenitor cells (DCPC) were assayed by their capacity to form granulocytes and macrophages in 7-day diffusion chamber (DC) cultures. Dose-response experiments showed that a plateau effect was obtained in vitro for HU concentrations above 1 mM, killing about 40% of regenerating progenitor cells or normal proliferative granulocytes. Similarly, a plateau effect was found for doses exceeding about 15 mg i.p., when lethal effects on 3-4 day DC cultures were measured. Time-response studies in vitro showed that about 60% of maximum killing was achieved after only 10 min, with a levelling off of the effect for exposure times between 1 and 3 h. Total depression of 3H-thymidine incorporation in DC cultures was achieved in less than 0.5 h, and subsided within 4-6 h, after one i.p. injection of 23 mg HU. HU had no appreciable effect on DCPC of adult normal marrow, but killed 15% of agar colony-forming cells.
在体内和体外研究了羟基脲（HU）对正常及再生小鼠骨髓的致死效应。通过在7天扩散盒（DC）培养物中形成粒细胞和巨噬细胞的能力来检测祖细胞（DCPC）。剂量反应实验表明，对于体外高于1 mM的HU浓度，可获得平台效应，杀死约40%的再生祖细胞或正常增殖的粒细胞。同样，当测量对3 - 4天DC培养物的致死效应时，发现超过约15 mg腹腔注射剂量也会出现平台效应。体外时间反应研究表明，仅10分钟后就可达到约60%的最大杀伤率，在1至3小时的暴露时间内效应趋于平稳。腹腔注射23 mg HU后，DC培养物中3H - 胸苷掺入的完全抑制在不到0.5小时内实现，并在4 - 6小时内消退。HU对成年正常骨髓的DCPC没有明显影响，但杀死了15%的琼脂集落形成细胞。
