Abstract
Fibroblast growth factors (FGFs) are a structurally related family of proteins and play important roles in numerous biological events, and are expected to be used for protecting various organs against radiation-induced injuries. Recently radioprotective agents that modify biological responses are eagerly desired. Here we summarize our study on FGFs as radioprotective agents and discuss their perspectives.
We have evaluated the effect of FGF1 on damage of intestinal crypts and bone marrow cells caused by gamma-ray (or X-ray) irradiation. We found that when administered to animals prior to exposure to a high dose of radiation, FGF1 reduced the intestinal damage with the highest effectiveness among several wild-type FGFs examined. However, structural instability of wild-type FGF1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. We have developed an FGF1:FGF2 chimera (FGFC) that demonstrates structural stability and independence from exogenous heparin for its optimal activity. When FGFC was intraperitoneally administered to BALB/c mice prior to whole body gamma-irradiation, survival of small intestine crypts was significantly enhanced, as compared to control mice. FGFC was superior to FGF1 in its protective activity determined by several protocols, including post-radiation administration. FGFC also reduced the radiation-induced damage to bone marrow cells.
These results indicate that FGFs, especially FGFC, are effective radioprotective agents, and prompts their use in clinical settings.
