Nikkels P G, de Jong J P, Ploemacher R E
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Leuk Res. 1987;11(9):817-25. doi: 10.1016/0145-2126(87)90066-x.
We have compared four assays to detect hemopoietic stromal damage induced by various cytostatic agents in young (4-week old) and adult (12-week old) mice. These assays included: (a) quantitation of the hemopoietic stem cell content of subcutaneously implanted spleens and femurs, (b) quantitation of fibroblastic colony-forming units per femur and spleen, (c) quantitation of the growth of normal hemopoietic progenitor cells in irradiated cytostatic drug-treated mice, and (d) measurement of splenic hemopoietic stem cell accumulation in response to bacterial lipopolysaccharide-induced hemopoietic stress. Busulfan caused a short- and long-term hemopoietic stromal defect. However, the four assays used showed different kinetics and severity of the stromal damage. Cyclophosphamide treatment resulted in a short-term stromal damage which was repaired within one week to three months, depending on the assay used. Methotrexate and vincristine did not cause long-term stromal damage as measured by the four assays used, whereas a short-term splenic stromal damage was detected using the subcutaneous implantation technique. No significant differences in stromal sensitivity to drug treatment were observed between young and adult mice. The presented data suggest that the four assays used to study stromal integrity measure different components of the hemopoietic microenvironment, and indicate that the use of a single assay may well lead to erroneous interpretations.
我们比较了四种检测方法，以检测不同细胞抑制剂对年轻（4周龄）和成年（12周龄）小鼠造血基质造成的损伤。这些检测方法包括：（a）皮下植入脾脏和股骨中造血干细胞含量的定量分析，（b）每根股骨和脾脏中成纤维细胞集落形成单位的定量分析，（c）经照射的细胞抑制剂处理小鼠中正常造血祖细胞生长的定量分析，以及（d）测量脾脏造血干细胞在细菌脂多糖诱导的造血应激反应中的积累情况。白消安会导致短期和长期的造血基质缺陷。然而，所使用的四种检测方法显示出基质损伤的动力学和严重程度各不相同。环磷酰胺治疗会导致短期的基质损伤，根据所使用的检测方法，这种损伤会在1周内至3个月内修复。甲氨蝶呤和长春新碱在所使用的四种检测方法中未导致长期的基质损伤，而使用皮下植入技术检测到了短期的脾脏基质损伤。在年轻和成年小鼠之间，未观察到基质对药物治疗的敏感性存在显著差异。所呈现的数据表明，用于研究基质完整性的四种检测方法测量的是造血微环境的不同组成部分，并表明使用单一检测方法很可能会导致错误的解释。
