Photodynamic inactivation of selected intracellular enzymes by hematoporphyrin derivative and their relationship to tumor cell viability in vitro.
The photosensitivity of freshly dissociated R3230AC mammary adenocarcinoma cells was examined by measurement of the activities of selected intracellular enzymes after treatment with hematoporphyrin derivative (Hpd) and exposure to light in vitro. Enzymes selected as representative of the cytosolic cell compartment showed no loss in activity, whereas malate dehydrogenase, located in the mitochondrial matrix, displayed a modest decrease (approximately 15%) in activity. In contrast, cytochrome c oxidase and succinate dehydrogenase, enzymes associated with the mitochondrial membrane, demonstrated a very rapid and more marked inhibition of activities, approximately 45% and 25%, respectively. The time-course of inhibition of these mitochondrial membrane enzymes preceded the loss of cell viability, which displayed slower kinetics as seen by a more gradual and progressive pattern of loss in viability. These data suggest that the mitochondria are an early-affected and important intracellular site for Hpd photosensitization.
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors; D005260:Female; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000633:toxicity*; D007700:Kinetics; D008027:Light; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D004791:Enzyme Inhibitors; D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017324:Hematoporphyrin Derivative