SUBCELLULAR PHOTOTOXICITY OF 5-AMINOLEVULINIC ACID (ALA)

Background and Objective: 5-aminolaevulinic acid (ALA) is a new, promi sing photosensitizer for PDT of cancer. Subcellular toxicity induced b y ALA and light exposure in single cells was studied to elucidate the mechanism of cell damage. Study Design/Materials and Methods: CPAE, PT K2, and rat neonatal myocardial cells treated with ALA were examined f or localization using fluorescence microscopy and for subcellular phot otoxicity using 630 nm laser microbeam irradiation of spe cific subcel lular regions. Results: In CPAE and PTK, cells, a large amount of fluo rescence was detected in the peri-nuclear cytoplasm. In rat neonatal m yocardial cells, the sensitizer selectively localized in the large mit ochondria. In both cell types, there was little phototoxicity when the peripheral cytoplasmic region was exposed, as compared to considerabl e phototoxicity with exposure of either the perinuclear or nuclear reg ions. Conclusion: Both the CPAE and PTK, cells demonstrated that the n ucleus followed by the perinuclear cytoplasm are the most sensitive ce ll areas with no sensitivity in the peripheral cytoplasm. (C) 1998 Wil ey-Liss, Inc.