Ultrastructural changes in PAM cells after photodynamic treatment with delta-aminolevulinic acid-induced porphyrins or photosan

Photodynamic therapy (PDT) is the combination of a photosensitizing drug (P s) with light in the presence of oxygen leading to the generation of reacti ve molecular species and destruction of cancer cells. In this study we comp ared PDT with two Ps, the hematoporphyrin derivative Photosan (Ph) and delt a-aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX, with resp ect to mitochondrial function and ultrastrucural alterations. The effects o f PDT were investigated in PAM 212 cells after different Ps incubation time s, light doses, and post-treatment periods, Both Ps induced a Light dose-de pendent impairment of the mitochondrial function with the dose-response cur ve being steep for ALA and flat for Ph, The prolongation of the incubation time from 4 to 20 h resulted in an increased reduction of mitochondrial act ivity after ALA PDT but not after Ph PDT, Treatment with an irradiation dos e that decreased mitochondrial activity by 50% (IC50) led to early and prof ound changes of mitochondrial morphology in ALA photosensitized cells, wher eas photosensitization with Ph resulted in more pronounced alterations of l ysosomes, We conclude that at bioequivalent sublethal PDT exposures of PAM 212 cells, ALA-induced damage is primarily restricted to mitochondria, wher eas Ph-induced cytotoxicity is mediated by damage of the lysosomal system.