PORPHYRINS, PORPHYRIAS, CANCER AND PHOTODYNAMIC THERAPY - A MODEL FORCARCINOGENESIS

Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand better the involvement of porphyrins in pho tosensitization reactions, the heme biosynthetic pathway is first desc ribed, as well as the main features of its regulation in both erythroi d and hepatic cells. Most disorders of porphyrin metabolism, known as porphyrias, are characterized by porphyrin accumulation. A full discus sion of these diseases, their classification and relevant biochemical and clinical signs are presented. Abnormalities in heme biosynthesis i n disorders other than porphyrias, such as iron-deficient and siderobl astic anemias, lead poisoning, hereditary tyrosinemia, chronic renal d isease and alcoholism, are briefly considered. A complete survey of th e experimental research on the biosynthesis of porphyrins in tumors an d of the important association between cancer and porphyrias is dealt with. The link to photodynamic therapy (PDT) emerges naturally and thi s is treated from the point of view of using porphyrins endogenously f ormed by the tumors for their localization and PDT. Finally, consideri ng the nature of the alterations occurring in heme metabolism in tumor s, and porphyrias and their ubiquity, a model is discussed where the a bnormality of heme synthesis is involved in the initiating lesion of c arcinogenesis. Tle model strongly predicts that the incidence of cance r will be high in cells with abnormal heme metabolism, suggesting that porphyric patients may be at greater risk of the development of cance r.