title: Role of p53 and ATM in photodynamic therapy-induced apoptosis.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy.
  
  
  METHODS
  We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting.
  
  
  RESULTS
  m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level.
  
  
  CONCLUSIONS
  p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Viola
authors.initials: V
authors.lastname: Heinzelmann-Schwarz
authors.forename: André
authors.initials: A
authors.lastname: Fedier
authors.forename: René
authors.initials: R
authors.lastname: Hornung
authors.forename: Heinrich
authors.initials: H
authors.lastname: Walt
authors.forename: Urs
authors.initials: U
authors.lastname: Haller
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D017353:Gene Deletion; D016158:Genes, p53 / Q000502:physiology*; D008652:Mesoporphyrins / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010778:Photochemotherapy; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011836:Radiation Tolerance / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; C072269:temoporfin