Particle irradiation induces FGF2 expression in normal human lens cells

Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-indu ced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associa ted with cataract. Normal human lens epithelial (HLE) cells were cultured i n vitro on extracellular matrix (ECM) originated from bovine corneal endoth elial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h aft er exposure to particle radiation, followed by another wave of increased tr anscription at 2-3 h postirradiation, Immunofluorescence results confirm th e enhanced levels of FGF2 protein rapidly after exposure to protons or heli um ions, followed by another wave of increased activity unique to helium at 6 h postirradiation, This second wave of increased immunoreactivity was no t observed in the proton-irradiated samples, Total FGF2 protein analysis af ter helium-ion exposures shows induced expression of three FGF2 isoforms, w ith an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-indu ced cataract are discussed. (C) 2000 by Radiation Research Society.