IN-VIVO RADIOPROTECTIVE EFFECTS OF ANGIOGENIC GROWTH-FACTORS ON THE SMALL-BOWEL OF C3H MICE

This study was undertaken to determine if acidic or basic fibroblast g rowth factor (FGF1 or FGF2) or vascular endothelial growth factor (VEG F) alters the radiation response of small bowel after total-body irrad iation (TBI). Female C3H mice were treated with various doses of angio genic growth factor administered intravenously 24 h before or 1 h afte r TBI. Radiation doses ranged from 7 to 18 Gy. End points measured wer e the number of crypts in three portions of the small bowel, the frequ ency of apoptosis of crypt cells at various times after TBI, and the L D,,,,, (bone marrow syndrome) and LD50/6 (GI syndrome). Fibroblast gro wth factors alone, without TBI, decreased the number of crypts per cir cumference significantly. Among the factors tested, FGF2 caused the gr eatest decline in baseline crypt number. Despite this decrease in the baseline crypt number, after irradiation the number of surviving crypt s was greater in animals treated with growth factor. The greatest radi oprotection occurred at intermediate doses of growth factor (6 to 18 m u g/mouse). Mice treated with FGF1 and FGF2 had crypt survival curves with a slope that was more shallow than that for saline-treated animal s, indicating radiation resistance of crypt stem cells in FOE-treated mice. The LD50/6 was increased by approximately 10% for all treatments with angiogenic growth factors, whether given before or after TBI. Ap optosis of crypt cells was maximum at 4 to 8 h after TBI. The cumulati ve apoptosis was decreased significantly in animals treated with angio genic growth factors, and the greatest protection against apoptosis wa s seen in animals treated with FGF2 prior to TBI. All three angiogenic growth factors tested were radioprotective in small bowel whether giv en 24 h before or 1 h after irradiation. The mechanism of protection i s unlikely to involve proliferation of crypt stem cells, but probably does involve prevention of radiation-induced apoptosis or enhanced rep air of DNA damage of crypt cells. (C) 1998 by Radiation Research Socie ty.