Induction by carbon-ion irradiation of the expression of vascular endothelial growth factor in lung carcinoma cells.
OBJECTIVE
To investigate the induction by carbon- ion irradiation of vascular endothelial growth factor (VEGF) mRNA and protein.


METHODS
RERF-LC-AI lung squamous carcinoma cells were irradiated with carbon ions of either 13.3, 50 or 90keV/microm. Colony formation was used to determine cell survival. VEGF mRNA and protein of the irradiated cells were quantified by Northern blot analysis and ELISA assay, respectively. Genistein, Src tyrosine kinase inhibitor and H7, protein kinase C inhibitor, were used to inhibit VEGF mRNA expression.


RESULTS
The relative biological effectiveness (RBE) of carbon ions (13.3, 50 and 90keV/microm) was 1.10, 1.97 and 2.30, respectively, in terms of D10 values. Single doses of 15 Gy with either X-rays or carbon ions significantly 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 protein levels, detected in culture supernatant 24h after irradiation with 50 and 90keV/microm carbon ions. Neither mRNA nor protein induction showed a dependence on LET. The induction of VEGF mRNA by carbon-ion irradiation was completely inhibited by pretreating cells with genistein and H7, indicating that Src tyrosine kinase and protein kinase C on cell surface membranes is involved in the induction.


CONCLUSIONS
Irradiation of lung carcinoma cells with carbon ions induced VEGF mRNA expression and increased protein levels. The induction was dose-dependent. Radiation-induced DNA damage and/or its repair may not be a prerequisite for the induction of VEGF mRNA.
Ando
S
S
International Space Radiation Laboratory, National Institute of Radiological Sciences, Chiba, Japan.
Nojima
K
K
Ishihara
H
H
Suzuki
M
M
Ando
M
M
Majima
H
H
Ando
K
K
Kuriyama
T
T
D002244:Carbon; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000528:radiation effects*; D020450:Heavy Ions; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D008222:Lymphokines / Q000096:biosynthesis* / Q000528:radiation effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002244:Carbon