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Role of p53 and ATM in photodynamic therapy‐induced apoptosis
Author(s) -
HeinzelmannSchwarz Viola,
Fedier André,
Hornung René,
Walt Heinrich,
Haller Urs,
Fink Daniel
Publication year - 2003
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.10213
Subject(s) - apoptosis , photodynamic therapy , programmed cell death , tunel assay , necrosis , cancer research , ataxia telangiectasia , uvb induced apoptosis , photosensitizer , trypan blue , microbiology and biotechnology , chemistry , biology , dna damage , caspase , biochemistry , dna , organic chemistry , genetics
Background and Objectives 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. Study Design/Materials and 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. Lasers Surg. Med. 33:182–189, 2003. © 2003 Wiley‐Liss, Inc.