Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus.
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.
Hinnen
P
P
Department of Gastroenterology & Hepatology (Internal Medicine II), University Hospital Rotterdam-Dijkzigt, The Netherlands.
de Rooij
F W
FW
van Velthuysen
M L
ML
Edixhoven
A
A
van Hillegersberg
R
R
Tilanus
H W
HW
Wilson
J H
JH
Siersema
P D
PD
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*
D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011163:Hydroxymethylbilane Synthase; D005294:Ferrochelatase