In vivo radioprotective effects of basic fibroblast growth factor (FGF2) in total body irradiated C3H/HeNCr mice

Fibroblast growth factor (FGF2) was recently found to radioprotect endothelial cells. We examined its in vivo radiomodifying effects on bone marrow in total body irradiated (TBI) mice. Female C3H/HeNCr mice were given FGF2 intravenously. Total FGF2 per mouse ranged from 1 to 24 μg, delivered 24 and 4 hr before TBI or 24 and 48 hr after irradiation. Histologic examinations were performed of the marrow and other organs, and serum cytokine levels of tumor necrosis factor-α (TNF-α), interleukin-3 (IL-3), and granulocyte-macrophage colony stimulating factor (GM-CSF) were determined from FGF2- or saline-treated mice with an enzyme-linked immunosorbent assay (ELISA) technique. FGF2 given pre-TBI significantly improved the survival of lethally irradiated mice. FGF2 radioprotection was dose-dependent and was maximized at a dose of 6 μg/mouse. The radiomodification was 1.16 ± 0.04 (±1 S.D.) with an increase of LD50/30 from 771 ± 10 to 891 ± 28 cGy. Some radiomodification was even observed when FGF2 was given 24 hr after irradiation (P < 0.05). FGF2 radioprotected mice through a mechanism that improved recovery of bone marrow hematopoietic cells. The absence of abnormal IL-3, GM-CSF, or TNF-α blood levels favors a direct proliferative effect on hematopoietic tissue rather than an indirect induction of cytokines. Other possible mechanisms of FGF2 action are discussed. Radiat Oncol Invest 1996;4:9–16. © 1996 Wiley-Liss, Inc.