Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus.

Abstract

Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX might be a suitable photosensitizer in Barrett's oesophagus and adenocarcinoma, we determined the activities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus. A PDT power index for ALA-induced porphyrin accumulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and premalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epithelium. A significantly increased PDT power index in Barrett's epithelium and adenocarcinoma was found. Our results suggest that, after the administration of ALA, porphyrins will accumulate in a greater amount in Barrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PBG-D and FC activities. The PDT power index here defined might be a useful indicative parameter for predicting the susceptibility of these tissues to ALA-PDT.

• Authors: P Hinnen, F W de Rooij, M L van Velthuysen, A Edixhoven, R van Hillegersberg, H W Tilanus, J H Wilson, P D Siersema
• Journal: British journal of cancer (Br J Cancer) Vol. 78 Issue 5 Pg. 679-82 (Sep 1998) ISSN: 0007-0920 [Print] England
• PMID: 9744510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents
• Prodrugs
• Protoporphyrins
• Aminolevulinic Acid
• protoporphyrin IX
• Hydroxymethylbilane Synthase
• Ferrochelatase

Topics

• Adult
• Aged
• Aminolevulinic Acid (pharmacology, therapeutic use)
• Barrett Esophagus (drug therapy, metabolism)
• Esophageal Neoplasms (drug therapy, metabolism)
• Esophagus (enzymology)
• Female
• Ferrochelatase (metabolism)
• Humans
• Hydroxymethylbilane Synthase (metabolism)
• Male
• Middle Aged
• Photochemotherapy
• Photosensitizing Agents
• Precancerous Conditions (drug therapy, metabolism)
• Prodrugs (therapeutic use)
• Protoporphyrins (biosynthesis)