Induction by carbon-ion irradiation of the expression of vascular endothelial growth factor in lung carcinoma cells

Purpose: To investigate the induction by carbon- ion irradiation of vascula r endothelial growth factor (VEGF) mRNA and protein. Materials and methods: RERF-LC-AI lung squamous carcinoma cells were irradi ated with carbon ions of either 13.3, 50 or 90 keV/mu m. Colony formation w as used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectiv ely. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhi bitor, were used to inhibit VEGF mRNA expression. Results: The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90 keV/mu m) was 1.10, 1.97 and 2.30, respectively, in terms of D-10 values. Single doses of 15 Gy with either X-rays or carbon ions significan tly induced VEGF mRNA expression at 16-24h after irradiation with a maximum induction of 2.81-fold. A significant increase was also observed in VEGF p rotein levels, detected in culture supernatant 24 h after irradiation with 50 and 90 keV/mu m carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation wa s completely inhibited by pretreating cells with genistein and H7, indicati ng that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction. Conclusion: Irradiation of lung carcinoma cells with carbon ions induced VE GF mRNA expression and increased protein levels. The induction was dose-dep endent. Radiation-induced DNA damage and/or its repair may not be a prerequ isite for the induction of VEGF mRNA.