FACTORS AFFECTING AMNINOLAEVULINIC ACID-INDUCED GENERATION OF PROTOPORPHYRIN-IX

Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing cellular hypoxia as a result of microcirculat ory shutdown. Aminolaevulinic acid (ALA) causes cellular accumulation of protoporphyrin IX (PPIX) in cells exposed to it in excess. PPIX can be used as a photosensitizer for PDT. Microcirculatory shutdown may b e induced by toxicity to the endothelial and vascular smooth muscle (V SM) cells or by release of vasoactive substances. We have studied whet her PPIX is produced by endothelial, VSM and tumour cells on exposure to ALA and whether these cell lines are directly damaged by PDT in vit ro. Tumour endothelial cells are angiogenic and we have, therefore, in vestigated the effect of cellular proliferation rates on PPIX generati on. Tumour cells generate more PPIX intracellularly than the non-neopl astic cell lines studied and are correspondingly more sensitive to PDT -induced cytotoxicity. Endothelial cells are sensitive to PDT-induced cytotoxicity and accumulate between 1.5 and four times more PPIX when proliferating (as during tumour-induced angiogenesis) than when quiesc ent. We conclude that PPIX-mediated PDT may exert some of its effects on the microcirculation of treated tissues by direct toxicity to enoth elial and VSM cells, and that this toxicity may be enhanced in the tum our microenvironment.