title: 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.affiliation: Department of Gastroenterology & Hepatology (Internal Medicine II), University Hospital Rotterdam-Dijkzigt, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Hinnen
authors.forename: F W
authors.initials: FW
authors.lastname: de Rooij
authors.forename: M L
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: A
authors.initials: A
authors.lastname: Edixhoven
authors.forename: R
authors.initials: R
authors.lastname: van Hillegersberg
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: J H
authors.initials: JH
authors.lastname: Wilson
authors.forename: P D
authors.initials: PD
authors.lastname: Siersema
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004947:Esophagus / Q000201:enzymology; D005260:Female; D005294:Ferrochelatase / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000378:metabolism; D011355:Prodrugs / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000096:biosynthesis*
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011163:Hydroxymethylbilane Synthase; D005294:Ferrochelatase