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A TEST OF THE SINGLET OXYGEN MECHANISM OF CATIONIC DYE PHOTOSENSITIZATION OF MITOCHONDRIAL DAMAGE
Author(s) -
Bunting James R.
Publication year - 1992
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1992.tb04212.x
Subject(s) - phototoxicity , photobleaching , singlet oxygen , photochemistry , chemistry , photosensitizer , cationic polymerization , fluorescence , mitochondrion , phosphorescence , inner mitochondrial membrane , oxygen , biophysics , rose bengal , membrane potential , organic chemistry , biochemistry , in vitro , biology , optics , physics
— Aromatic cationic dyes have a potential as photo‐chemotherapeutic agents because they are selectively concentrated into the mitochondria of cancerous cells. The mechanism of cytophototoxicity has been proposed to be primarily due to dye sensitized photogeneration of highly toxic singlet oxygen ( 1 O 2 ) at the mitochondria. We tested this hypothesis by measuring the relative phototoxicity of a collection of aromatic cationic dyes towards respiring rat‐liver mitochondria (RLM), upon addition of 514 nm laser light. Effectiveness of dye photosensitization towards destruction of RLM function was assayed by its effect on the RLM membrane potential. Three physical parameters of dye phototoxicity were independently measured and a relative phototoxicity calculated assuming adherence of mechanism to the 1 O 2 hypothesis. Quantum yields of dye sensitized 1 O 2 production were estimated, either from time‐resolved luminescence measurements of photosensitized 1 O 2 formed, or by comparing rates of photobleaching of 1 O 2 trap; the relative partition of dye into mitochondrial lipid was determined gravimetrically; and the optical density of dye was determined in a lipid like Triton X‐100 micellar environment. Under the assumption of the 1 O 2 hypothesis, these parameters were used to predict a relative phototoxicity which was compared with that observed. For 12 of the 14 dyes investigated, the observed and predicted phototoxicities were linearly correlated (r=0.85) suggesting support of the 1 O 2 hypothesis. Carbocyanines DiOC2(3) and DiSC2(3) did not correlate and were found to be 10 and 1000 times more potent than predicted, suggesting an additional factor at play in their phototoxicity.