In vivo Radioprotective Effects of Basic Fibroblast Growth Factor in C3H Mice

Kim, Yeon Shil; Yoon, Sei Chul

Abstract

PURPOSE: In order to understand in vivo radiation damage modifying effect of bFGF on jejunal mucosa, bone marrow and the effect of bFGF on the growth of transplanted mouse sarcoma 180 tumor in mice.
MATERIALS AND METHODS
Mice were treated with 6 microgram of bFGF at 24 hours and 4 hours before exposing to 600 cGy, 800 cGy and 1,000 cGy total body irradiation (TBI), and then exposed to 3,000 cGy local radiation therapy on the tumor bearing thigh. Survival and tumor growth curve were plotted in radiation alone group and combined group of bFGF and irradiation (RT). Histologic examination was performed in another experimental group. Experimental groups consisted of normal control, tumor control, RT (radiation therapy) alone, 6 microgram bFGF alone, combined group of 3 microgram bFGF and irradiation (RT), combined group of 6 microgram bFGF and irradiation (RT). Histologic examination was performed with H-E staining in marrow, jejunal mucosa, lung and sarcoma 180 bearing tumor. Radiation induced apoptosis was determined in each group with the DNA terminal transferase nick-end labeling method (ApopTag S7100-kit, Intergen Co.)
RESULTS
The results were as follows 1) 6 microgram bFGF given before TBI significantly improved the survival of lethally irradiated mice. bFGF would protect against lethal bone marrow syndrome. 2) 6 microgram bFGF treated group showed a significant higher crypt depth and microvilli length than RT alone group (p<0.05). 3) The bone marrow of bFGF treated group showed less hypocellularity than radiation alone group on day 7 and 14 after TBI (p<0.05), and this protective effect was more evident in 6 microgram bFGF treated group than that of 3 microgram bFGF treated group. 4) bFGF protected against early radiation induced apoptosis in intestinal crypt cell but might have had no antiapoptotic effect in bone marrow stem cell and pulmonary endothelial cells. 5) There was no significant differences in tumor growth rate between tumor control and bFGF alone groups (p>0.05). 6) There were no significant differences in histopathologic findings of lung and mouse sarcoma 180 tumor between radiation alone group and bFGF treated group.
CONCLUSIONS
Our results suggest that bFGF protects small bowel and bone marrow from acute radiation damage without promoting the inoculated tumor growth in C3H mice. Improved recovery of early responding normal tissue and reduced number of radiation induced apoptosis may be possible mechanism of radioprotective effect of bFGF.