Inhibition of FGF-1-induced mitogenesis in vitro and angiogenesis
by potassium 2,5-dihydroxyphenyl sulfonate (DHPS) and potassium 2,5-diacetoxyphenyl sulfonate (DAPS). Panel A shows the inhibition of mitogenesis induced by fibroblast growth factor (FGF)-1 in quiescent Balb/c 3T3 fibroblasts treated with DHPS or DAPS. Representative microphotographs show how oral administration of the vehicle alone (VEH; tap water: B), DHPS (300 mg/kg/day; eq. to 1.32 mmol/kg/d; C) and DAPS (300 mg/kg/day; eq. to 0.96 mmol/kg/d; D) affect FGF-1-induced angiogenesis in gelatin sponges subcutaneously implanted in rats for 7 days. In the same assay, intense leukocyte extravasation and infiltration can be observed in sponges containing FGF-1 when they are removed from vehicle-treated rats (E) but not from DAPS-treated rats (F). The extent of neovascularization detected in phosphate buffered saline (PBS)- and FGF-1-containing sponges removed from rats treated with vehicle, DHPS or DAPS can be quantified (G). In a separate assay (H) the dose-response relationship of the effects of orally administered DAPS is shown (20 to 300 mg/kg/day; eq. to 0.06 to 0.96 mmol/kg/d), expressing the data as the mean ± SEM number of functional vessels per field, determined in 6 randomly acquired fields per specimen. The number of rats used for each measurement is indicated in parentheses: ***p < 0.001 vs. neovascularization in the absence of FGF-1; ††† p < 0.001 vs. FGF-1 + VEH; §§ p < 0.01 vs. FGF-1 + DHPS by one-factor ANOVA followed by Student-Newmann-Keuls test. Magnifications: B-D, x200; E-F, x400.