Nikkels P G, de Jong J P, Ploemacher R E
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Br J Haematol. 1988 Jan;68(1):3-9. doi: 10.1111/j.1365-2141.1988.tb04171.x.
We studied the short- and long-term effects of a fractionated injection of cis-diamminedichloroplatinum (II) (CDDP) upon the haemopoietic stroma and the haemopoietic precursor cell compartment of young and adult mice. The integrity of the stromal microenvironment was investigated using three different assays including quantification of (a) the fibroblastoid progenitor cell compartment, (b) the regenerative capacity after subcutaneous implantation of spleen and femur, and (c) the growth of normal bone marrow progenitors in lethally irradiated CDDP-treated mice. CDDP treatment induced a slight anaemia which lasted for the observation period of 1 year, and could not be restored by infusion of normal bone marrow cells. The population size of haemopoietic progenitors was severely decreased immediately after CDDP treatment and the CFU-S recovery in the bone marrow was slow and temporary. Stromal function was significantly decreased and normalization occurred within approximately 40 d, depending on the stromal parameter measured. Subsequently, the regenerative capacity of the stroma showed a second decrease which was still detected at 1 year. This pattern of stromal damage has not been reported for any other cystostatic agent. Since the other two assays did not detect a second decrement in stromal integrity it is implied that the three stromal assays used detect different stromal functions. We conclude that CDDP treatment of both young and adult mice results in severe short-term damage and a late occurring secondary regenerative defect of the haemopoietic organ stroma.
我们研究了分次注射顺二氯二氨铂（II）（CDDP）对幼年和成年小鼠造血基质及造血前体细胞区室的短期和长期影响。使用三种不同的检测方法研究了基质微环境的完整性，包括对（a）成纤维细胞样祖细胞区室进行定量分析、（b）皮下植入脾脏和股骨后的再生能力以及（c）在接受致死性照射的CDDP处理小鼠中正常骨髓祖细胞的生长情况。CDDP处理诱发了轻度贫血，该贫血在1年的观察期内持续存在，且输注正常骨髓细胞无法使其恢复。造血祖细胞的群体数量在CDDP处理后立即显著减少，骨髓中CFU-S的恢复缓慢且呈暂时性。基质功能显著下降，约40天内恢复正常，具体取决于所测量的基质参数。随后，基质的再生能力出现第二次下降，在1年时仍可检测到。尚未有其他任何一种细胞抑制剂出现这种基质损伤模式的报道。由于其他两种检测方法未检测到基质完整性的第二次下降，这意味着所使用的三种基质检测方法检测到的是不同的基质功能。我们得出结论，对幼年和成年小鼠进行CDDP处理会导致造血器官基质严重的短期损伤以及后期出现的继发性再生缺陷。
