Photodynamic therapy (
PDT) is a new treatment modality for solid
tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5-aminolevulinic
acid-induced
protoporphyrin IX (
PPIX) shows important advantages over other
photosensitizers, the main mechanisms of
phototoxicity induced are still poorly understood. Three human colon
carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of
photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular
photosensitizer localization on efficiency of
PDT were examined, and cellular parameters after
PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between
PDT-induced apoptosis from
necrosis. The fibroblast cell line was less affected by
phototoxicity than the
tumor cells to a variable degree. Well-differentiated
tumor cells showed higher toxicity than less-differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial
PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane-bound
PPIX induces a loss of membrane integrity and consequent
necrosis. Although the absolute amount of intracellular
photosensitizer concentration plays the main determining role for
PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage.