Relationship of mitochondrial function and cellular adenosine triphosphate levels to hematoporphyrin derivative-induced photosensitization in R3230AC mammary tumors.
The effects of hematoporphyrin derivative-induced photosensitization on the levels of adenosine triphosphate (ATP) in R3230AC mammary adenocarcinomas were studied. Enzymatically dissociated tumor cells were exposed to various doses of hematoporphyrin derivative (HPD) in vitro plus photoradiation. A drug and light dose-dependent decrease in cellular ATP levels was observed; ATP levels were reduced by 60% after treatment with 7.0 micrograms HPD per ml plus 0.72 J total energy density per cm2. Cell viability, assessed by exclusion of trypan blue, displayed an apparently coordinate behavior to ATP levels. The effects of hematoporphyrin derivative plus photoradiation were examined in the presence of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation, or iodoacetate, an inhibitor of glycolysis, experiments designed to elucidate the site of action leading to reduced ATP levels. The results indicated that HPD-induced photosensitization had little additive effects to oligomycin-sensitive ATP production, whereas significant further reduction in ATP levels was obtained by HPD-induced photosensitization in the presence of iodoacetate. Taken together, along with earlier studies of selected mitochondrial enzymes, we conclude that HPD plus photoradiation inhibits mitochondrial function leading to reduction in cellular ATP levels and loss of viability.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006414:Hematoporphyrin Photoradiation; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010778:Photochemotherapy; D051381:Rats
D007461:Iodoacetates; D009840:Oligomycins; D000255:Adenosine Triphosphate; D019807:Iodoacetic Acid