Tumor Growth and Tumor Radiosensitivity in Mice Given Myeloprotective Doses of Fibroblast Growth Factors

Background: Radiation at doses high enough to cure cancer also frequently destroys normal tissue. Development of agents that protect normal tissue without also protecting diseased tissue has been difficult. In vivo radioprotection of bone marrow by acidic and basic fibroblast growth factors (FGF1 and FGF2, respectively) has recently been demonstrated after whole-body irradiation of C3H/HeN mice. Purpose: Our purpose was to determine whether myeloprotective doses of those growth factors also protect malignant tumors. Methods: First, we investigated the effects of exogenous FGF1 or FGF2 (FGF1/2) administration (treatment group receiving two intravenous injections of 3 μg FGF1/2 per mouse 24 hours and 4 hours before local irradiation of right hind leg and control group receiving two intravenous injections of 0.1 mL of saline) on growth and radiosensitivity of three transplantable murine tumors (one squamous cell carcinoma [SCC-VII] and two sarcomas [KHT and Rif-1]), all of which were grown in C3H/HeN mice. We then evaluated the effect of FGF1/2 on tumor cell proliferation, cell cycle distribution, and pulmonary metastatic frequency in the mice. Specifically, survival studies were performed in mice treated with 0, 6, 6.5, 7.5, 8.5, 9, or 10 Gy whole-body irradiation with or without FGF2 (n = 250). Rif-1 (n = 40), KHT (n = 40), and SCC-VII (n = 40) tumors were implanted in the hind leg of mice, and mice were treated with FGF2 or saline when their tumor-bearing thighs were 9 mm in diameter. In separate experiments (treatment group receiving two injections of 3 μg each of FGF2 [6 μg total] either intravenously or intratumorally 24 hours and 4 hours before local tumor irradiation and control group receiving 0.1 mL saline), tumor growth was followed, and mice were killed to count lung metastases and measure tumor proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine labeling at various times thereafter (three to eight mice per group). Tumor growth curves of untreated and irradiated tumors were determined with and without intravenous or intratumoral FGF1/2 in SCC-VII tumors (n = 120). Radiation doses to the tumor-bearing leg were 15 and 30 Gy for SCC-VII, 30 Gy for Rif-1, and 15 Gy for KHT. From each experiment, the mean (±1 standard error) was calculated from data obtained from three to 20 mice. Statistical tests used included two-tailed Student's t test, the chi-squared test, and Fisher's exact test. All P values represent two-tailed tests of statistical