1 May 1995 Mechanisms of phototoxicity catalyzed by two porphycenes
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Abstract
The porphycenes represent a new class of photosensitizing agent with enhanced absorbance in the red. We examined the photodynamic effects of two porphycenes, a monomer and a pyrazine-linked dimer, using the P388 murine leukemia and P388/ADR, a subline that expresses the multidrug-resistance phenotype. The monomer localized at mitochondrial loci while the dimer photosensitized lysosomes and the cell membrane. the dimer was more phototoxic in terms of cells killed and photons absorbed, perhaps because of the difference in localization sites. Phototoxic effects of both porphycenes could be abolished by the addition of the oxygen scavenger trolox (a vitamin E analog) during irradiation. Both porphycenes were recognized by the multidrug transporter, an outward transport process associated with multidrug resistance. Photodynamic actio of the porphycenes in cell culture was associated with apoptosis, resulting in DNA fragmentation. Inhibition of phospholipase C activity prevented initiation of apoptosis after irradiation without protecting cells from photodamage at sites of sensitizer localization. At high concentrations, the porphycenes exhibit a 'dark toxicity' that also was associated with apoptosis, but subsequent irradiation abolished apoptosis, perhaps via destruction of endonucleases, and only necrotic cell death was observed.
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David Kessel, David Kessel, Yu Luo, Yu Luo, Kathryn W. Woodburn, Kathryn W. Woodburn, Chi Kwong Chang, Chi Kwong Chang, Barbara W. Henderson, Barbara W. Henderson, } "Mechanisms of phototoxicity catalyzed by two porphycenes", Proc. SPIE 2392, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IV, (1 May 1995); doi: 10.1117/12.208180; https://doi.org/10.1117/12.208180
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