Porphyrin biosynthesis in human Barrett's oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid.
5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis, which is used for ALA-based photodynamic therapy (ALA-PDT), was studied in tissues of 10 patients with Barrett's oesophagus (BE) and adenocarcinoma of the oesophagus (AC) undergoing oesophagectomy at a mean time interval of 6.7 h after the ingestion of ALA (60 mg kg(-1)). In BE, AC, squamous epithelium (SQ) and gastric cardia, the activities of the haem biosynthetic enzymes porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) and the PDT power index--the ratio between PBG-D and FC in BE and AC in comparison with SQ--were determined before ALA ingestion. Following ALA administration, ALA, porphobilinogen, uroporphyrin I and PPIX were determined in tissues and plasma. The PDT power index did not predict the level of intracellular accumulation of PPIX found at 6.7 h. In BE, there was no selectivity of PPIX accumulation compared to SQ, whereas in half of patients with AC selectivity was found. Higher haem biosynthetic enzyme activities (i.e. PBG-D) and lower PPIX precursor concentrations were found in BE and AC compared to SQ. It is therefore possible that PPIX levels will peak at earlier time intervals in BE and AC compared to SQ.
Hinnen
P
P
Department of Gastroenterology and Internal Medicine II, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
de Rooij
F W
FW
Terlouw
E M
EM
Edixhoven
A
A
van Dekken
H
H
van Hillegersberg
R
R
Tilanus
H W
HW
Wilson
J H
JH
Siersema
P D
PD
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001471:Barrett Esophagus / Q000188:drug therapy / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005294:Ferrochelatase / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011162:Porphobilinogen / Q000097:blood / Q000378:metabolism; D011166:Porphyrins / Q000096:biosynthesis* / Q000097:blood; D011524:Protoporphyrins / Q000096:biosynthesis / Q000097:blood
D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011163:Hydroxymethylbilane Synthase; D005294:Ferrochelatase