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 oesophagu s (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 (Sa) and g astric cardia, the activities of the haem biosynthetic enzymes porphobilino gen 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 deter mined before ALA ingestion. Following ALA administration, ALA, porphobilino gen, uroporphyrin I and PPIX were determined in tissues and plasma. The PDT power index did not predict the level of intracellular accumulation of PPI X found at 6.7 h. In BE, there was no selectivity of PPIX accumulation comp ared to SQ, whereas in half of patients with AC selectivity was found. High er haem biosynthetic enzyme activities (i.e. PBG-D) and lower PPIX precurso r concentrations were found in BE and AC compared to SQ, It is therefore po ssible that PPIX levels will peak at earlier time intervals in BE and AC co mpared to SQ. (C) 2000 Cancer Research Campaign.