Comparison of delta-aminolaevulinic acid and its methyl ester as an inducer of porphyrin synthesis in cultured cells.
This study was carried out to test the hypothesis that induction of intracellular porphyrin synthesis by delta-aminolaevulinic acid (ALA) used to sensitize cells in photodynamic therapy would be more efficient if the ALA was used in an esterified form. Contrary to expectation, the generation of tetrapyrroles (TP) by cultured epithelial cells (CNCM-I-221) exposed to equimolar concentrations (0.6 mM) of ALA or its methyl ester (ALA-ME) showed that the mean total TP production rate during 6 h incubation in serum-free medium was 0.13 fmol cell(-1) h(-1) for ALA-exposed cells compared with 0.04 fmol cell(-1) h(-1) for cells exposed to ALA-ME. Fluorescein diacetate uptake and conversion to fluorescein indicated intracellular non-specific esterase activity, implying that ALA-ME conversion to ALA can occur. Cells exposed to ALA-ME exhibited loss of a greater proportion of total tetrapyrroles in the form of extracellular protoporphyrin IX (PPIX; 22.8%) compared with 11.6% in ALA-treated cells with a corresponding reduction in cell-associated PPIX (P < 0.05). A variable initial elevation in haem levels in ALA-ME-treated cells was observed, but did not reach statistically significant levels.
Washbrook
R
R
Department of Molecular Pathology, UCL Medical School, London, UK.
Riley
P A
PA
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000096:biosynthesis*; D051381:Rats; D013268:Stimulation, Chemical
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX