Witte L, Fuks Z, Haimovitz-Friedman A, Vlodavsky I, Goodman D S, Eldor A
Arteriosclerosis Research Center, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Cancer Res. 1989 Sep 15;49(18):5066-72.
The effects of radiation on the release of mitogenic factors into the media of cultured endothelial cells of bovine, porcine, and human origins were studied. Although unirradiated controls revealed a significant background activity, single doses of irradiation (20-60 Gy) resulted in a dose-related increased release of growth factor activity, measured by the mitogenic effects of the conditioned media on both 3T3 mouse fibroblasts and unirradiated endothelial cells serving as target cells. Receptor binding competition assays for the platelet-derived growth factor receptor revealed that 12-28% of the total mitogenic activity was due to platelet-derived growth factor-like mitogens. Mitogenic assays using endothelial cells and specific antibody mediated inhibition assays suggested that another component of the mitogenic activity was due to a fibroblast growth factor-like factor. Although radiation resulted in a significant increase in cell death, the enhanced growth factor activities did not appear to result from cell lysis-related leakage of intracellular stores of growth factor. Instead, our data suggest that the growth factors were synthesized de novo and secreted at elevated levels by the cells which maintained postradiation a high level of metabolic activity. Time course studies demonstrated that the growth factors accumulation in the conditioned media started within the first 24 h after radiation and reached a plateau within 72 h after treatment. Radiation-induced release of endothelial cell-derived growth factors may be involved in the pathogenesis of both early vascular damage and the late fibrosis which represents a prominent feature of late radiation damage in normal tissues.
研究了辐射对牛、猪和人源培养内皮细胞培养基中促有丝分裂因子释放的影响。尽管未辐照的对照组显示出显著的背景活性，但单剂量辐照（20 - 60 Gy）导致生长因子活性的释放呈剂量依赖性增加，这是通过条件培养基对3T3小鼠成纤维细胞和作为靶细胞的未辐照内皮细胞的促有丝分裂作用来测量的。针对血小板衍生生长因子受体的受体结合竞争试验表明，总促有丝分裂活性的12 - 28%归因于血小板衍生生长因子样促有丝分裂原。使用内皮细胞的促有丝分裂试验和特异性抗体介导的抑制试验表明，促有丝分裂活性的另一个成分归因于成纤维细胞生长因子样因子。尽管辐射导致细胞死亡显著增加，但生长因子活性的增强似乎并非源于与细胞裂解相关的细胞内生长因子储存的泄漏。相反，我们的数据表明，生长因子是重新合成的，并由在辐射后保持高水平代谢活性的细胞以升高的水平分泌。时间进程研究表明，条件培养基中生长因子的积累在辐射后的最初24小时内开始，并在处理后72小时内达到平台期。辐射诱导的内皮细胞衍生生长因子的释放可能参与早期血管损伤和晚期纤维化的发病机制，晚期纤维化是正常组织晚期辐射损伤的一个突出特征。
