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Biosynthesis and photodynamic efficacy of protoporphyrin IX (PpIX) generated by 5-aminolevulinic acid (ALA) or its hexylester (hALA) in rat bladder carcinoma cells.

Abstract
Hexylester of 5-aminolevulinic acid (hALA) has been considered as an alternative to 5-aminolevulinic acid (ALA) for the treatment of malignancies of different origin. The present study addresses the ALA and hALA-induced PpIX pharmacokinetic profile using rat bladder carcinoma cells (AY27). The total PpIX content measured spectrofluorimetrically after extraction procedure at the end of 2 h incubation was at least 1.5-fold greater with hALA compared to ALA despite the difference in concentration of several orders between the two compounds (1 or 5 mM ALA and 5 or 10 x 10(-3) mM hALA). Considerable PpIX efflux was detected in the extracellular medium at the end of the incubation. With 5 mM ALA and 10 x 10(-3) mM hALA, PpIX build-up was continued beyond the incubation period pointing out to enzyme saturation in the biosynthetic pathway or/and the constitution of ALA reserve. Red laser light (lambda=630 nm) irradiation of AY27 cells after 2 h incubation with increasing ALA or hALA concentrations resulted in a nearly equal photocytotoxicity.
AuthorsI Cosserat-Gerardin, L Bezdetnaya, D Notter, C Vigneron, F Guillemin
JournalJournal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 59 Issue 1-3 Pg. 72-9 (Dec 2000) ISSN: 1011-1344 [Print] Switzerland
PMID11332893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Extracts
  • Culture Media
  • Culture Media, Serum-Free
  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX
Topics
  • Aminolevulinic Acid (pharmacology)
  • Animals
  • Cell Extracts
  • Cell Survival
  • Culture Media
  • Culture Media, Serum-Free
  • Dose-Response Relationship, Drug
  • Fluorescence
  • Photochemotherapy (methods)
  • Photosensitizing Agents (pharmacokinetics, pharmacology)
  • Protoporphyrins (biosynthesis, pharmacokinetics, pharmacology)
  • Rats
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms (drug therapy)

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