title: Effect of radiation on vascular endothelial growth factor expression in the C2 canine mastocytoma cell line.
abstract: OBJECTIVE
  To establish the radiosensitivity and effect of irradiation on vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) expression in the canine mastocytoma cell line C2.
  
  
  METHODS
  Canine mastocytoma cell line C2.
  
  
  METHODS
  C2 cells were irradiated with single doses of 2, 4, 6, and 8 Gy. The 3-(4, 5-di-methyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and proliferation assays with (methyl-hydrogen 3) thymidine were used for radiosensitivity experiments. Expression of VEGFR was determined via flow cytometry and apoptotic rate via annexin assay. Human and canine VEGF ELISA kits were evaluated in crossover assay experiments, and the canine kit was used thereafter.
  
  
  RESULTS
  C2 cells secreted VEGF constitutively. Radiation did not induce a significant increase in VEGF secretion, regardless of radiation dose. Consistently, radiation did not up-regulate VEGFR. Cell survival rates decreased in a dose-dependent manner. The apoptotic cell fraction had a dose-dependent increase that reached its maximum 24 to 48 hours after radiation.
  
  
  CONCLUSIONS
  The C2 cell line was radiosensitive, and a fraction (up to 40%) of cells died via apoptosis in a dose-dependent manner. In response to radiation, C2 cells did not upregulate VEGF production or VEGFR. Further studies are needed to determine whether tumor control could be improved by combining radiotherapy with VEGFR inhibitors or apoptosis-modulating agents.
authors.affiliation: Division of Small Animal Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna 1210, Austria.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sekis
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Gerner
authors.forename: Michael
authors.initials: M
authors.lastname: Willmann
authors.forename: Laura
authors.initials: L
authors.lastname: Rebuzzi
authors.forename: Alexander
authors.initials: A
authors.lastname: Tichy
authors.forename: Martina
authors.initials: M
authors.lastname: Patzl
authors.forename: Johann G
authors.initials: JG
authors.lastname: Thalhammer
authors.forename: Armin
authors.initials: A
authors.lastname: Saalmüller
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Kleiter
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics; D017209:Apoptosis / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000473:pathology / Q000532:radiotherapy*; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D012515:Mast-Cell Sarcoma / Q000473:pathology / Q000532:radiotherapy / Q000662:veterinary*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
chemical_list: D017304:Annexin A5; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1