Role of p53 and ATM in photodynamic therapy-induced apoptosis.
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.
Heinzelmann-Schwarz
Viola
V
Department of Obstetrics and Gynecology, Division of Gynecology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Fedier
André
A
Hornung
René
R
Walt
Heinrich
H
Haller
Urs
U
Fink
Daniel
D
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
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