EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR ON IN-VIVO CEREBRAL TUMORIGENESIS IN RATS

OBJECTIVE: In vitro evidence suggests that basic fibroblast growth fac tor (bFGF) promotes tumor cell proliferation and angiogenesis. In this study, we evaluated the early and delayed effects of recombinant huma n bFGF on the early and late phases of in vivo, in situ tumorigenesis in rats. METHODS: Brain tumors were induced by transplacentally exposi ng fetal rats to N-nitrosoethylurea on Day 17 of pregnancy. On postnat al (PN) Day 60 or 90, N-nitrosoethylurea-exposed rats underwent stereo tactic intraventricular implantation of Gelfoam saturated with bFGF (6 0 mu g) or vehicle; the rats were killed 4 days (early group) or 30 da ys (delayed group) later. The early and delayed effects of bFGF on the early phase of tumorigenesis (PN Day 60) were evaluated in 14 and 10 rats, respectively; early and delayed effects on the late phase of tum origenesis (PN Day 90) were evaluated in 12 rats each. RESULTS: Histol ogical examination 30 days after implantation showed a significantly h igher tumor rate in rats that had been treated with bFGF on PN Day 90, compared with vehicle-treated control rats (P < 0.05); furthermore, i n the bFGF-treated animals there was significantly greater intratumora l and periventricular glial fibrillary acidic protein expression, as d etermined immunohistochemically. Increased vascularity in the tumor ip silateral to the implant was found in 2 of 14 rats that had been treat ed with bFGF on PN Day 60. CONCLUSION: These findings support in vitro evidence that bFGF and its receptor complex are implicated in the gen esis and progression of N-nitrosoethylurea-induced brain tumors in thi s animal model.