Delta-aminolevulinic acid as a photosensitizer precursor for the treatment of hepatoma cells in vitro

Mark A. Laukka, Kenneth K. Wang

Research output: Contribution to journalConference article

Abstract

Delta-aminolevulinic acid (δ-ALA) has been recently proposed as a tumor photosensitizer precursor with increased selectivity and decreased toxicity for the treatment of neoplasms. Aims: We investigated the conversion and cytotoxicity of δ-ALA in a human hepatoma cell line to determine its clinical potential. Methods: SK-HEP- 1 (ATCC) cells were plated on 35 mm coverslips in media for use in a digital fluorescence microscopic imaging system. δ-ALA was added to achieve fmal concentrations between 0-S mM. Cells were excited with 450-490 nm light while a 610 nm long pass filter was used to assess fluorescence from conversion to protoporphyrin IX, the putative photosensitizer. After maximal fluorescence was obtained at each initial concentration of a-ALA, cells were radiated with 10 J/cm2 of light from a xenon lamp fitted with a 515 nm band pass filter. After photoradiation, cell death was assessed by flow cytometry using propidium iodide labeling. Results: Protoporphyrin IX accumulation was constant at Ks=0.001 until a plateau was achieved 2 hours after the addition of δ-ALA. Photoradiation with 10 J/cm2 at a concentration of 1 mM δ-ALA resulted in a linear increase in cell death over time with 5% cell death at 2 hours (p < 0.05) and 12% at 5 hours (p < 0.01) compared to controls. Interestingly, controls with δ-ALA alone demonstrated a cytoprotective effect with a logarithmic relationship between increasing cell survival and increasing dose of drug (r2 =0.97). Conclusions: Fluorescence measurements indicate that maximum cellular content of protoporphyrin IX occurs 2 hours after administration of δ-ALA to hepatoma cells with a rate constant of 0.001. Photoradiation produces a small but significant increase in cell death. The use of δ-ALA as a photosensitizer precursor in hepatoma cells appears to be limited by the conversion rate and a possible cytoprotective effect.

Original languageEnglish (US)
Pages (from-to)60-68
Number of pages9
JournalProceedings of SPIE - The International Society for Optical Engineering
Volume2133
DOIs
StatePublished - Jul 19 1994
EventOptical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III 1994 - Los Angeles, United States
Duration: Jan 23 1994Jan 29 1994

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering

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