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 language | English (US) |
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Pages (from-to) | 60-68 |
Number of pages | 9 |
Journal | Proceedings of SPIE - The International Society for Optical Engineering |
Volume | 2133 |
DOIs | |
State | Published - Jul 19 1994 |
Event | Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III 1994 - Los Angeles, United States Duration: Jan 23 1994 → Jan 29 1994 |
ASJC Scopus subject areas
- Electronic, Optical and Magnetic Materials
- Condensed Matter Physics
- Computer Science Applications
- Applied Mathematics
- Electrical and Electronic Engineering