Effects of basic fibroblast growth factor on in vivo cerebral tumorigenesis in rats.

OBJECTIVE In vitro evidence suggests that basic fibroblast growth factor (bFGF) promotes tumor cell proliferation and angiogenesis. In this study, we evaluated the early and delayed effects of recombinant human bFGF on the early and late phases of in vivo, in situ tumorigenesis in rats. METHODS Brain tumors were induced by transplacentally exposing fetal rats to N-nitrosoethylurea on Day 17 of pregnancy. On postnatal (PN) Day 60 or 90, N-nitrosoethylurea-exposed rats underwent stereotactic intraventricular implantation of Gelfoam saturated with bFGF (60 micrograms) or vehicle; the rats were killed 4 days (early group) or 30 days (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 tumorigenesis (PN Day 90) were evaluated in 12 rats each. RESULTS Histological examination 30 days after implantation showed a significantly higher tumor rate in rats that had been treated with bFGF on PN Day 90, compared with vehicle-treated control rats (P < 0.05); furthermore, in the bFGF-treated animals there was significantly greater intratumoral and periventricular glial fibrillary acidic protein expression, as determined immunohistochemically. Increased vascularity in the tumor ipsilateral to the implant was found in 2 of 14 rats that had been treated with bFGF on PN Day 60. CONCLUSION These findings support in vitro evidence that bFGF and its receptor complex are implicated in the genesis and progression of N-nitrosoethylurea-induced brain tumors in this animal model.