MITOCHONDRIAL PHOTOSENSITIZATION BY PHOTOFRIN II |
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Authors: | Gurmit Singh W Patrick Jeeves Brian C Wilson Daniel Jang |
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Institution: | Ontario Cancer Treatment and Research Foundation, and McMaster University, Hamilton, Canada |
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Abstract: | Abstract V-79 Chinese hamster cells grown as monolayers or as multicell spheroids were treated with Photofrin II (10 μ.g m−1 for 16 h) and various doses of red light irradiation. The resulting biochemical and functional damage to cell mitochondria was studied. The activities of both succinic dehydrogenese and cytochrome c oxidase were found to decrease in a light dose-dependent manner. The respiratory control quotient (RC) decreased in parallel with a decrease in the activities of the respiratory chain proteins. Our data also showed a distinct temporal difference in the relative progression of mitochondrial damage and cell death as assessed by loss of discrete Rhodamine-123 (Rh-123) localization and trypan blue infiltration, respectively. Mitochondrial damage was detected immediately, as seen by derealization of Rh-123 resulting from dissipation of the electrochemical gradient in damaged mitochondria. Trypan blue infiltration occurs with a distinct time lag. These findings are consistent with the hypothesis that, at least for long Photofrin II incubation times, the mitochondrion is a primary target of photosensitization. The subsequent changes in cell membrane permeability may be a delayed result of decreased bioenergetics of the Photofrin II photosensitized cell. |
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