title: Inactivation of ataxia telangiectasia mutated gene can increase intracellular reactive oxygen species levels and alter radiation-induced cell death pathways in human glioma cells.
abstract: OBJECTIVE
  To investigate the effects of ataxia telangiectasia mutated (ATM)-regulated reactive oxygen species (ROS) and cell death pathways on the response of U87MG glioma cells to ionising radiation (IR) and oxidative stress.
  
  
  METHODS
  ATM expression was blocked in U87MG glioma cells using a small interfering RNA (siRNA) technique. Cell survival, sub-lethal damage (SLD), and potential lethal damage (PLD) repair following IR were assessed by clonogenic assay while changes in intracellular ROS, the apoptosis, and autophagy were followed by flow cytometry and Western blotting.
  
  
  RESULTS
  Blocking ATM expression in U87MG cells increased intracellular ROS levels and sensitivity to the cytotoxic effects of IR and oxygen stress; effects that could be partly counteracted by the antioxidant N-acetylcysteine (NAC). Knock down of ATM rendered cells unable to repair sub-lethal or potentially lethal damage and DNA double strand breaks (DSB) after IR exposure; something that NAC could not counteract. ATM did control the pathways a cell used to die following IR and this did seem to be ROS-dependent.
  
  
  CONCLUSIONS
  ATM is involved in redox control but ROS elevations following ATM knock down seem more involved in the decision as to what cell death pathway is utilised after IR than DSB repair and radiosensitivity.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 101 Sec. 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Wang
authors.forename: Chu-Chiao
authors.initials: CC
authors.lastname: Wu
authors.forename: Yuan-Yaw
authors.initials: YY
authors.lastname: Wei
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.forename: Chi-Shiun
authors.initials: CS
authors.lastname: Chiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020868:Gene Silencing; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases