Porphyrin biosynthesis in human Barrett's oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid

Br J Cancer. 2000 Aug;83(4):539-43. doi: 10.1054/bjoc.2000.1300.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / adverse effects
  • Aminolevulinic Acid / pharmacokinetics
  • Aminolevulinic Acid / pharmacology*
  • Barrett Esophagus / drug therapy
  • Barrett Esophagus / metabolism*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / metabolism*
  • Female
  • Ferrochelatase / metabolism
  • Heme / metabolism
  • Humans
  • Hydroxymethylbilane Synthase / metabolism
  • Male
  • Middle Aged
  • Photochemotherapy / methods*
  • Photosensitizing Agents / adverse effects
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / pharmacology*
  • Porphobilinogen / blood
  • Porphobilinogen / metabolism
  • Porphyrins / biosynthesis*
  • Porphyrins / blood
  • Protoporphyrins / biosynthesis
  • Protoporphyrins / blood


  • Photosensitizing Agents
  • Porphyrins
  • Protoporphyrins
  • Heme
  • Porphobilinogen
  • Aminolevulinic Acid
  • protoporphyrin IX
  • Hydroxymethylbilane Synthase
  • Ferrochelatase