Goff J P, Shields D S, Boggs S S, Greenberger J S
Department of Radiation Oncology, University of Pittsburgh Cancer Institute Pennsylvania, USA.
Radiat Res. 1997 Jan;147(1):61-9.
The role of recombinant hematopoietic growth factors in radiation repair has become a subject of increasing interest in both clinical and basic radiobiology. Combinations of cytokines such as hepatocyte growth factor, interleukin (IL)-3, IL-11, kit ligand, GM-CSF and erythropoietin were used to study the in vitro radiation dose response of human cord blood CD34+ hematopoietic progenitor cells using clonogenic survival assays. CD34+ cells were isolated by immunomagnetic selection and irradiated at 8 cGy/min. Irradiated cells were plated in methylcellulose with or without added cytokines, and hematopoietic colonies including CFU-GM, BFU-E and CFU-GEMM were scored on day 14. The radiation response characteristics of BFU-E and CFU-GEMM were similar for all culture conditions tested. The D0 values for BFU-E ranged between 1.29 and 2.40 Gy and n between 1.0 and 1.4. The D0 values for CFU-GEMM ranged from 86 cGy to 2.02 Gy and n between 1.0 and 1.5. The D0 for CFU-GM grown without added factors was 1.03 Gy. With single cytokine stimulation (IL-3, IL-11 or varying concentrations of HGF), D0 values ranged from 1.11 to 1.44 Gy. With the combination of IL-3, GM-CSF, kit ligand and HGF, D0 values were not significantly altered and ranged between 1.61 and 2.60 Gy. In contrast, the combination of IL-11 and HGF produced an increase in the shoulder of the radiation survival curve (n = 3.35). No increase in the shoulder was detected for any of the other conditions tested (n = 1.0-1.7). Thus the combination of HGF and IL-11 increased the radiation survival of hematopoietic progenitor cells forming CFU-GM. Understanding the mechanism by which combinations of early-acting growth factors support postirradiation recovery of primitive clonogenic hematopoietic cells may be relevant to the design of clinical protocols for improving hematopoietic recovery after total-body irradiation.
重组造血生长因子在辐射修复中的作用已成为临床和基础放射生物学领域日益关注的课题。使用集落形成存活试验，将肝细胞生长因子、白细胞介素（IL）-3、IL-11、kit配体、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和促红细胞生成素等细胞因子组合，来研究人脐血CD34+造血祖细胞的体外辐射剂量反应。通过免疫磁珠分选分离出CD34+细胞，并以8 cGy/分钟的剂量进行照射。将照射后的细胞接种于添加或不添加细胞因子的甲基纤维素中，在第14天对包括粒-巨噬细胞集落形成单位（CFU-GM）、红系爆式集落形成单位（BFU-E）和粒-红-巨噬-巨核系集落形成单位（CFU-GEMM）在内的造血集落进行计数。在所有测试的培养条件下，BFU-E和CFU-GEMM的辐射反应特征相似。BFU-E的D0值在1.29至2.40 Gy之间，n在1.0至1.4之间。CFU-GEMM的D0值在86 cGy至2.02 Gy之间，n在1.0至1.5之间。未添加因子培养的CFU-GM的D0为1.03 Gy。在单一细胞因子刺激（IL-3、IL-11或不同浓度的肝细胞生长因子）下，D0值在1.11至1.44 Gy之间。在IL-3、GM-CSF、kit配体和肝细胞生长因子的组合作用下，D0值无显著变化，在1.61至2.60 Gy之间。相比之下，IL-11和肝细胞生长因子的组合使辐射存活曲线的肩区增大（n = 3.35）。在测试的任何其他条件下均未检测到肩区增大（n = 1.0 - 1.7）。因此，肝细胞生长因子和IL-11的组合提高了形成CFU-GM的造血祖细胞的辐射存活率。了解早期作用生长因子组合支持照射后原始集落形成造血细胞恢复的机制，可能与设计改善全身照射后造血恢复的临床方案相关。
