Reversible effects of photodamage directed toward mitochondria.
When the initial effect of photodynamic therapy (PDT) involves mitochondrial photodamage, an early effect is loss of the mitochondrial membrane potential (ΔΨm ). Using murine hepatoma 1c1c7 cells and a photosensitizing agent known to target mitochondria, we examined loss of ΔΨm , initiation of apoptosis and loss of viability as a function of time and light dose. There was a correlation between loss of viability and the rapid disappearance of ΔΨm, as detected by the potential-sensitive probe Mitotracker Orange (MTO). Loss of ΔΨm was, however, reversible even with a substantial loss of viability. Unless there was a supralethal level of photodamage, 1c1c7 cells recovered their mitochondrial membrane potential, even if the cell population was on the pathway to apoptosis and cell death. These results indicate that when mitochondria are the initial PDT target, a qualitative estimate of photokilling can be provided by assessing the initial loss of ΔΨm.
Department of Pharmacology, Wayne State University, Detroit, MI.
David
D
Kessel
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D000077362:Verteporfin; D014966:Xanthenes
D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; D014966:Xanthenes; C121372:mitotracker orange; D000077362:Verteporfin