title: Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.
abstract: The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer.
authors.affiliation: Photonics Research Ontario, Department of Medical Biophysics and, Ontario Cancer Institute, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9.
authors.forename: L
authors.initials: L
authors.lastname: Lilge
authors.forename: M
authors.initials: M
authors.lastname: Portnoy
authors.forename: B C
authors.initials: BC
authors.lastname: Wilson
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017323:Dihematoporphyrin Ether / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D007211:Indoles; D008652:Mesoporphyrins; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C044797:chloroaluminum phthalocyanine; D000622:Aminolevulinic Acid; D017323:Dihematoporphyrin Ether; C028025:protoporphyrin IX; C072269:temoporfin