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Effect of ionizing radiation on thymidine uptake, differentiation, and VEGFR2 receptor expression in endothelial cells: the role of VEGF(165).
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2001 May 01; Vol. 50 (1), pp. 213-20. - Publication Year :
- 2001
-
Abstract
- Purpose: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of beta ionizing radiation on human EC viability, thymidine uptake, and differentiation.<br />Methods and Materials: Endothelial cells were exposed to (32)P-labeled DNA oligonucleotides 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.<br />Results: A dose-dependent inhibitory effect of beta irradiation on ECs' thymidine 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 the 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 were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs.<br />Conclusions: beta irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF(165), an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation.
- Subjects :
- Adenoviruses, Human genetics
Beta Particles
Cell Differentiation radiation effects
Cell Division radiation effects
Cell Survival radiation effects
Cells, Cultured
Endothelial Growth Factors biosynthesis
Endothelial Growth Factors genetics
Endothelial Growth Factors metabolism
Endothelium, Vascular cytology
Endothelium, Vascular metabolism
Humans
Lymphokines biosynthesis
Lymphokines genetics
Lymphokines metabolism
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular physiology
Muscle, Smooth, Vascular virology
Receptor Protein-Tyrosine Kinases genetics
Receptors, Growth Factor genetics
Receptors, Vascular Endothelial Growth Factor
Up-Regulation radiation effects
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Endothelial Growth Factors physiology
Endothelium, Vascular radiation effects
Lymphokines physiology
Receptor Protein-Tyrosine Kinases biosynthesis
Receptors, Growth Factor biosynthesis
Thymidine pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0360-3016
- Volume :
- 50
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 11316566
- Full Text :
- https://doi.org/10.1016/s0360-3016(01)01445-6