Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: The role of VEGF(165)

Purpose: Late thrombosis of irradiated vascular segments may be the consequ ence of endothelial cell (EC) dysfunction after radiation therapy. We inves tigated the effects of beta ionizing radiation on human EC viability thymid ine uptake, and differentiation. Methods and Materials: Endothelial cells were exposed to P-32-labeled DNA o ligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF(165) on these functions were assayed. Results: A dose-dependent inhibitory effect of beta irradiation on ECs' thy midine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy, VEGF(165) proved to have a radioprotective effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in th e presence of 10 ng/ml of VEGF(165) (p < 0.05 vs. LacZ), This concentration of VEGF(165) also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects wer e in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs, Conclusions: <beta> irradiation interacts directly with EC functions by sig nificantly reducing their ability to differentiate and proliferate, associa ted with upregulation of VEGFR2, These effects can be prevented in part by pretreating cells with VEGF(165), an effect potentially favored by the upre gulation of VEGFR2 receptor expression after irradiation, (C) 2001 Elsevier Science Inc.