Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue

The apoptotic response of normal brain and intracranial VX2 tumour followin g photodynamic therapy (PDT) mediated by 5 different photosensitizers (Phot ofrin. 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chlor oaluminium phthalocyanine (AlClPc). Tin Ethyl Etiopurpupin (SnET2), and met a-tetra(hydroxyphenyl)chlorin (mTHPC)) was evaluated following a previous a nalysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apo ptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transfe rase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis an d determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinka ge, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any d etectable apoptosis, while the other photosensitizers produced Varying numb ers of apoptotic cells near the region of coagulative necrosis. The apoptot ic response did not appear to be related to photosensitizer dose. These res ults suggest that at this time point, a minimal and fairly localized apopto tic effect is produced in brain tissues, the extent of which depends largel y on the particular photosensitizer, (C) 2000 Cancer Research Campaign.