Abstract
An FGF1:FGF2 chimera (FGFC) was created previously and showed greater structural stability than FGF1. FGFC was capable of stimulating epithelial cell proliferation much more strongly than FGF2 even in the absence of heparin. Therefore, FGFC was expected to have greater biological activity in vivo. This study evaluated and compared the protective activity of FGFC and FGF1 against the radiation-induced intestinal injuries. FGFC and FGF1 were administered intraperitoneally to BALB/c mice 24 h before or after total body irradiation (TBI). The surviving numbers of crypts per circumference were determined 3.5 days after TBI with γ-rays at doses ranging from 8 to 12 Gy. When 10 μg of each FGF was administered without heparin 24 h before irradiation, FGFC was more effective in promoting crypt survival than FGF1, although the effect of FGFC was equal to or slightly superior to FGF1 with heparin. FGFC was effective in promoting crypt survival even when it was administered without heparin at 24 h after TBI at a dose of 10, 11, or 12 Gy, whereas FGF1 did not increase crypt survival under these conditions. FGFC post-treatment promoted prominent BrdU incorporation into crypts, epithelial differentiation, and increased crypt depth. However, the number of apoptotic cells in FGFC-treated mice decreased to almost the same level as 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.
