Ding I, Wu T, Matsubara H, Magae J, Shou M, Cook J, Okunieff P
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cytokine. 1997 Jan;9(1):59-65. doi: 10.1006/cyto.1996.0136.
Basic fibroblast growth factor is known to stimulate the proliferation of bone marrow stem and/or progenitor cells in vitro and in vivo. We examined a similar cytokine, acidic fibroblast growth factor (FGF1), for its in vivo radiomodifying effects. Female C3H/HeNCr mice were given human recombinant FGF1 intravenously at doses ranging from 1 to 24 micrograms. FGF1 was delivered in two equal doses 24 and 4 h before or 24 h after otherwise lethal total body irradiation (TBI). In vivo FGF1 radioprotection of C3H mice was maximized at a total dose of 12 micrograms/mouse given before TBI. The radiomodification was 1.16 +/- 0.03 (+/- 1 SD) with an increase of LD50/30 from 736 +/- 9 to 854 +/- 16 cGy (P < 0.01). Some retroactive radiomodification was observed even when FGF1 was given 24 h after irradiation (P < 0.05). FGF1 radioprotected mice by improving the repopulation of haematopoietic progenitor cells of bone marrow. The radioprotection was not associated with an increase in S-phase fraction or detectable circulating IL-3, TNF-alpha or GM-CSF, suggesting that other mechanisms of protection were responsible.
已知碱性成纤维细胞生长因子可在体外和体内刺激骨髓干细胞和/或祖细胞的增殖。我们研究了一种类似的细胞因子,即酸性成纤维细胞生长因子(FGF1)的体内辐射修饰作用。给雌性C3H/HeNCr小鼠静脉注射剂量范围为1至24微克的人重组FGF1。FGF1在致死性全身照射(TBI)前24小时和4小时或照射后24小时分两次等量给药。在TBI前给C3H小鼠静脉注射12微克/只的FGF1时,其体内辐射防护效果最佳。辐射修饰系数为1.16±0.03(±1标准差),LD50/30从736±9 cGy增加到854±16 cGy(P<0.01)。即使在照射后24小时给予FGF1,也观察到了一定的延迟辐射修饰作用(P<0.05)。FGF1通过改善骨髓造血祖细胞的再增殖来对小鼠起到辐射防护作用。这种辐射防护作用与S期细胞比例的增加或可检测到的循环IL-3、TNF-α或GM-CSF无关,提示存在其他保护机制。