Rebischung J L, Gougeon M D, Mori K J, Lemaigre G, Mathé G, Jasmin C
Cancer Res. 1984 Feb;44(2):503-6.
A previous study using a single injection of (chloro-2-ethyl)ribofuranosyl-3-nitrosourea has indicated the low acute hematotoxicity of this nitrosourea. However, because the hematotoxicity of nitrosourea is usually cumulative, we have studied the effect of injecting (chloro-2-ethyl)ribofuranosyl-3-nitrosourea (15 mg/kg) dissolved in 0.2 ml sterile oil C57BL X i.p. into DBA/2F1 mice for 5 consecutive weeks. The dose per injection represents the minimal dose necessary to show the maximal therapeutic efficacy on L1210 leukemia. Bone marrow cellularity and histology, spleen weight, bone marrow and splenic pluripotent stem cells, and colony-forming units committed to granulocyte-macrophage differentiation were measured 1, 2, 4, 7, and 14 days after the last injection in treated and control mice receiving oil only. No morphological or histological changes were found in the spleen and bone marrow of treated mice. In both organs, the number of splenic pluripotent hematopoietic stem cells decreased by about 1 log 1 day after the last injection but rapidly returned to normal values on Days 4 to 14. Granulocyte-macrophage-committed precursors were affected in both organs, at 20% of control values for bone marrow and 5% of control values for spleen on Day 1, with a transient and partial recovery on Day 4 followed by a second drop to 20 and 25% on Day 14. This effect on granulocyte-macrophage precursors contrasts with the absence of significant effect when the same treatment is used on peripheral white blood cell counts. Our results demonstrate that (chloro-2-ethyl)ribofuranosyl-3-nitrosourea belongs to the class of new nitrosoureas with low cumulative hematotoxicity.
一项先前使用单次注射（氯 - 2 - 乙基）呋喃核糖基 - 3 - 亚硝基脲的研究表明，这种亚硝基脲的急性血液毒性较低。然而，由于亚硝基脲的血液毒性通常具有累积性，我们研究了将溶解于0.2 ml无菌油中的（氯 - 2 - 乙基）呋喃核糖基 - 3 - 亚硝基脲（15 mg/kg）腹腔注射到DBA/2F1小鼠体内连续5周的效果。每次注射的剂量代表对L1210白血病显示最大治疗效果所需的最小剂量。在最后一次注射后的1、2、4、7和14天，对接受注射处理的小鼠和仅接受油注射的对照小鼠测量骨髓细胞密度和组织学、脾脏重量、骨髓和脾脏多能干细胞以及定向于粒细胞 - 巨噬细胞分化的集落形成单位。在接受处理的小鼠的脾脏和骨髓中未发现形态学或组织学变化。在两个器官中，脾脏多能造血干细胞数量在最后一次注射后1天减少约1个对数，但在第4至14天迅速恢复到正常水平。粒细胞 - 巨噬细胞定向前体细胞在两个器官中均受到影响，骨髓在第1天为对照值的20%，脾脏在第1天为对照值的5%，第4天有短暂部分恢复，随后在第14天再次降至20%和25%。这种对粒细胞 - 巨噬细胞前体细胞的影响与相同处理对外周白细胞计数无显著影响形成对比。我们的结果表明，（氯 - 2 - 乙基）呋喃核糖基 - 3 - 亚硝基脲属于具有低累积血液毒性的新型亚硝基脲类。
