APOPTOSIS IS AN EARLY EVENT DURING PHTHALOCYANINE PHOTODYNAMIC THERAPY-INDUCED ABLATION OF CHEMICALLY-INDUCED SQUAMOUS PAPILLOMAS IN MOUSE SKIN

Photodynamic therapy (PDT) is a promising new modality to treat malign ant neoplasms including superficial skin cancers, In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has sh own promising results both in in vitro assays and in implanted tumors, In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablat ion was also obtained, The Pc 4 was administered through tail vein inj ection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped d ye laser tuned at 675 nm for a total light dose of 135 J/cm(2), Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT, As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosi n staining and direct immunoperoxidase detection of digoxigenin-labele d genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%, The apoptotic bodies, as evident by the condensation of chromatin material around the perip hery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues fo llowing Pc 4 PDT, The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT, Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin canc er, and that apoptosis is an early event during this process.