title: An accelerated senescence response to radiation in wild-type p53 glioblastoma multiforme cells.
abstract: OBJECTIVE
  Radiotherapy is one of the few treatment options available for glioblastoma multiforme (GBM); however, the basis for its overall ineffectiveness in GBM is not fully understood. The present study was designed to explore the nature of the response to ionizing radiation in GBM cells to gain insight into the basis for the general failure of radiotherapy in the treatment of this disease.
  
  
  METHODS
  The response to fractionated radiotherapy was examined in GBM cell lines with differing p53 status. A viable cell number was determined during an 8-day period; accelerated senescence was based on beta-galactosidase staining and cell morphology; apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and fluorescence-activated cell-sorter analysis, whereas the expression of cell-cycle regulatory proteins was monitored by Western blot analysis. Based on clonogenic survival, the wild-type p53 U87 cells and mutant p53 T98 cells demonstrated essentially identical sensitivity to fractionated radiotherapy; however, neither cell line underwent apoptosis, and the primary response to irradiation was growth arrest. The wild-type p53 GBM cells showed clear evidence of accelerated senescence in response to irradiation. In contrast, senescence was not evident in mutant p53 GBM cells or GBM cells in which p53 function was abrogated by the viral E6 protein. The T98 (mutant p53) cells demonstrated a relatively robust proliferative recovery whereas both the rate and extent of recovery were attenuated in the wild-type p53 U87 cells.
  
  
  CONCLUSIONS
  Both accelerated senescence and conventional growth arrest are likely to represent alternative responses to apoptosis in irradiated GBM cells.
authors.affiliation: Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Quincy A
authors.initials: QA
authors.lastname: Quick
authors.forename: David A
authors.initials: DA
authors.lastname: Gewirtz
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D020127:Recovery of Function / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53