title: Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments.
abstract: OBJECTIVE
  Mesenchymal stem cells isolated from bone marrow (BM-MSC) and periodontal ligament (PLSC) are cells with high proliferative potential and ability to self-renewal. Characterization of these cells under genotoxic stress conditions contributes to the assessment of their prospective usage. The aim of our study was to evaluate changes in BM-MSC and PLSC caused by ionizing radiation.
  
  
  METHODS
  Human BM-MSC and PLSC were irradiated with the doses up to 20 Gy by Co(60) and observed 13 days; viability, proliferation, apoptosis and senescence induction, and changes in expression and phosphorylation status of related proteins were studied.
  
  
  RESULTS
  Irradiation with the doses up to 20 Gy significantly reduces proliferation, but has no significant effect on cell viability. The activation of tumor suppressor protein 53 (p53) and its phosphorylations on serines 15 and 392 were detected from the first day after irradiation by 20 Gy and remained elevated to day 13. Expression of cyclin-dependent kinases inhibitor 1A (p21(Cip1/Waf1)) increased. The cell cycle was arrested in G2 phase. Instead of apoptosis we have detected hallmarks of stress-induced premature senescence: increase in cyclin-dependent kinases inhibitor 2A (p16(INK4a)) and increased activity of senescence-associated β-galactosidase.
  
  
  CONCLUSIONS
  Mesenchymal stem cells isolated from bone marrow and periodontal ligament respond to ionizing radiation by induction of stress-induced premature senescence without apparent differences in their radiation response.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Prague.
authors.forename: Jana
authors.initials: J
authors.lastname: Cmielova
authors.forename: Radim
authors.initials: R
authors.lastname: Havelek
authors.forename: Tomas
authors.initials: T
authors.lastname: Soukup
authors.forename: Alena
authors.initials: A
authors.lastname: Jiroutová
authors.forename: Benjamin
authors.initials: B
authors.lastname: Visek
authors.forename: Jakub
authors.initials: J
authors.lastname: Suchánek
authors.forename: Jirina
authors.initials: J
authors.lastname: Vavrova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mokry
authors.forename: Darina
authors.initials: D
authors.lastname: Muthna
authors.forename: Lenka
authors.initials: L
authors.lastname: Bruckova
authors.forename: Stanislav
authors.initials: S
authors.lastname: Filip
authors.forename: Denis
authors.initials: D
authors.lastname: English
authors.forename: Martina
authors.initials: M
authors.lastname: Rezacova
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D017209:Apoptosis / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D010513:Periodontal Ligament / Q000166:cytology*; D010766:Phosphorylation / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D020169:Caspases