title: Characterization of DNA damage-induced cellular senescence by ionizing radiation in endothelial cells.
abstract: OBJECTIVE
  Inhibition of growth in mammalian cells in response to damage or stress is known as cellular senescence. Increasing evidence suggests that double-strand breaks (DSB) commonly mediate cellular senescence. Recently, radiation exposure has been reported to induce premature senescence.
  
  
  METHODS
  We investigated whether ionizing radiation (IR) at 4 Gy induces cellular senescence with DNA damage response in human umbilical vein endothelial cells (HUVEC). To determine alterations in gene expression on IR exposure, we have developed a DNA microarray analysis system that contains genes known to be involved in replicative senescence.
  
  
  RESULTS
  The damage by IR exposure is shown to result in a variety of senescence-like phenotypes such as changes in cell morphology, decrease in cell proliferation, increase in senescence- associated β-galactosidase (SA-β-gal) staining, and suppression of angiogenic activity. Moreover, the expression levels of several genes associated with cell cycle regulation are remarkably increased in IR-exposed endothelial cells. We found that IGFBP5 (insulin-like growth factor binding protein 5), PLAT (plasminogen activator), SNAI2 (snail homolog 2), JAG1 (jagged 1), SPRY4 (Sprouty homolog 4), and CD44 were upregulated, whereas CFB (complement factor B), VCAM1 (vascular cell adhesion molecule 1), AQP1 (aquaporin 1), LOXL1 (lysyl oxidase-like 1), and RBPMS (RNA-binding protein with multiple splicing) were down- regulated in both radiation-damaged and old cells.
  
  
  CONCLUSIONS
  These results imply that the IR-induced phenotype may be enhanced by alterations in genes associated with senescence.
authors.affiliation: Divisions of Radiation Effects.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Kim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kyu Jin
authors.initials: KJ
authors.lastname: Choi
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Bae
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Kim
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology* / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology* / Q000528:radiation effects*; D005312:Fetal Blood / Q000166:cytology* / Q000528:radiation effects; D006801:Humans; D011829:Radiation Dosage
chemical_list: D018797:Cell Cycle Proteins