Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan.
Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):860-7. doi: 10.1016/j.ijrobp.2010.04.045. Epub 2010 Aug 21.
A fibroblast growth factor (FGF) 1-FGF2 chimera (FGFC) was created previously and showed greater structural stability than FGF1. This chimera was capable of stimulating epithelial cell proliferation much more strongly than FGF1 or FGF2 even without heparin. Therefore FGFC was expected to have greater biologic activity in vivo. This study evaluated and compared the protective activity of FGFC and FGF1 against radiation-induced intestinal injuries.
We administered FGFC and FGF1 intraperitoneally to BALB/c mice 24 h before or after total-body irradiation (TBI). The numbers of surviving crypts were determined 3.5 days after TBI with gamma rays at doses ranging from 8 to 12 Gy.
The effect of FGFC was equal to or slightly superior to FGF1 with heparin. However, FGFC was significantly more effective in promoting crypt survival than FGF1 (p < 0.01) when 10 μg of each FGF was administered without heparin before irradiation. In addition, FGFC was significantly more effective at promoting crypt survival (p < 0.05) than FGF1 even when administered without heparin at 24 h after TBI at 10, 11, or 12 Gy. We found that FGFC post treatment significantly promoted 5-bromo-2'-deoxyuridine incorporation into crypts and increased crypt depth, resulting in more epithelial differentiation. However, the number of apoptotic cells in FGFC-treated mice decreased to almost the same level as that in FGF1-treated mice.
These findings suggest that FGFC strongly enhanced radioprotection with the induction of epithelial proliferation without exogenous heparin after irradiation and is useful in clinical applications for both the prevention and post treatment of radiation injuries.
先前创建了一种成纤维细胞生长因子（FGF）1-FGF2 嵌合体（FGFC），其结构稳定性优于 FGF1。该嵌合体即使没有肝素也能比 FGF1 或 FGF2 更强烈地刺激上皮细胞增殖。因此，FGFC 在体内具有更强的生物学活性。本研究评估并比较了 FGFC 和 FGF1 对辐射诱导的肠道损伤的保护作用。
我们在全身照射（TBI）前 24 小时或后，通过腹腔内给予 FGFC 和 FGF1 至 BALB/c 小鼠。用 γ 射线以 8 至 12 Gy 的剂量照射后 3.5 天，用 γ 射线测定存活隐窝的数量。
FGFC 的作用与肝素结合的 FGF1 相等或略优。然而，当在照射前没有肝素时，给予每种 FGF10μg，FGFC 促进隐窝存活的效果明显优于 FGF1（p<0.01）。此外，FGFC 在 TBI 后 24 小时没有肝素时，在 10、11 或 12 Gy 时，促进隐窝存活的效果明显优于 FGF1（p<0.05）。我们发现 FGFC 后处理显著促进了 5-溴-2'-脱氧尿苷掺入隐窝并增加了隐窝深度，从而促进了更多的上皮分化。然而，FGFC 处理组小鼠的凋亡细胞数量减少到与 FGF1 处理组小鼠几乎相同的水平。
这些发现表明，FGFC 在照射后没有外源性肝素的情况下，强烈增强了上皮细胞增殖的放射防护作用，在预防和治疗辐射损伤方面具有临床应用价值。
