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Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand ... more Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand better the involvement of porphyrins in photosensitization reactions, the heme biosynthetic pathway is first described, as well as the main features of its regulation in both erythroid and hepatic cells. Most disorders of porphyrin metabolism, known as porphyrias, are characterized by porphyrin accumulation. A full discussion of these diseases, their classification and relevant biochemical and clinical signs are presented. Abnormalities in heme biosynthesis in disorders other than porphySias, such as iron-deficient and sideroblastic anemias, lead poisoning, hereditary tyrosinemia, chronic renal disease and alcoholism, are briefly considered. A complete survey of the experimental research on the biosynthesis of porphyrins in tumors and of the important association between cancer and porphyrias is dealt with. The link to photodynamic therapy (PDT) emerges naturally and this is treated from the point of view of using porphyrins endogenously formed by the tumors for their localization and PDT. Finally, considering the nature of the alterations occurring in heme metabolism in tumors, and porphyrias and their ubiquity, a model is discussed where the abnormality of heme synthesis is involved in the initiating lesion of carcinogenesis. The model strongly predicts that the incidence of cancer will be high in cells with abnormal heme metabolism, suggesting that porphyric patients may be at greater risk of the development of cancer. Keywora!~: Porphyrins; Porphyrias; Cancer; Carcinogenesis; Photodynamic therapy loll-1344/93/$24.00 0 1993 -Elsevier Sequoia. All rights reserved A.M. de1 C. Bat& / Po~hyrins, porphytias, cancer and PDT 7 2.3. Regulation
Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand ... more Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand better the involvement of porphyrins in photosensitization reactions, the heme biosynthetic pathway is first described, as well as the main features of its regulation in both erythroid and hepatic cells. Most disorders of porphyrin metabolism, known as porphyrias, are characterized by porphyrin accumulation. A full discussion of these diseases, their classification and relevant biochemical and clinical signs are presented. Abnormalities in heme biosynthesis in disorders other than porphySias, such as iron-deficient and sideroblastic anemias, lead poisoning, hereditary tyrosinemia, chronic renal disease and alcoholism, are briefly considered. A complete survey of the experimental research on the biosynthesis of porphyrins in tumors and of the important association between cancer and porphyrias is dealt with. The link to photodynamic therapy (PDT) emerges naturally and this is treated from the point of view of using porphyrins endogenously formed by the tumors for their localization and PDT. Finally, considering the nature of the alterations occurring in heme metabolism in tumors, and porphyrias and their ubiquity, a model is discussed where the abnormality of heme synthesis is involved in the initiating lesion of carcinogenesis. The model strongly predicts that the incidence of cancer will be high in cells with abnormal heme metabolism, suggesting that porphyric patients may be at greater risk of the development of cancer. Keywora!~: Porphyrins; Porphyrias; Cancer; Carcinogenesis; Photodynamic therapy loll-1344/93/$24.00 0 1993 -Elsevier Sequoia. All rights reserved A.M. de1 C. Bat& / Po~hyrins, porphytias, cancer and PDT 7 2.3. Regulation