Hematoporphyrin derivative (HpD), a complex mixture of porphyrins, has been shown to preferentially localize in neoplastic tissue. It is this property which is the basis for both tumors localization and treatment since porphyrin laden tumor fluoresce when exposed to ultraviolet light and undergo necrosis when exposed to high intensity visible light. Neoplasms for which porphyrin detection and photoradiation therapy should be clinically useful include those which can be visualized endoscopically, e.g. bladder, bronchus,and larynx. Neither the mechanism of porphyrin tumor localization nor cytotoxicity have been completely elucidated. Indeed, the complexity of the porphyrin mixture in HpD, the most widely studied photosensitizer, has created challenging research problems in the identification of the """"""""active component"""""""" of HpD. Recent studies in our laboratory have documented a rapid and profound decrease in tumor blood flow to transplantable bladder tumors treated with HpD photoradiation therapy. Our studies suggest that disruption of tumor blood flow may be an important mechanism of action of this form of cancer therapy. In this proposal, we have outlined additional studies to clarify the effect of porphyrin--light induced ischemia on tumor cell death. Characterization of this effect is of importance since other antineoplastic treatment modalities (e.g. radiotherapy and chemotherapy) which can potentially be combined with photoradiation therapy are influenced by tumor blood flow. The effect of HpD-photoradiation therapy on non-neoplastic tissue and specifically on normal blood flow has not been investigated. These are of considerable importance since toxicity to normal tissue will limit the usefulness of this treatment modality. This proposal addresses this problem by studying the effect of HpD photoradiation on normal rat intestine.
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