LIPID-PEROXIDATION INDUCED BY A NOVEL PORPHYRIN PLUS LIGHT IN ISOLATED-MITOCHONDRIA - POSSIBLE IMPLICATIONS IN PHOTODYNAMIC THERAPY

With a view to locate porphyrins for use in photodynamic therapy (PDT) , the new modality of cancer treatment we have evaluated the ability o f a novel water soluble porphyrin o-tetrakis[4-(carboxymethyleneoxy)ph enyl]porphyrin (T4CPP) to induce damage to mitochondria during photose nsitization. T4CPP, when exposed to visible light, induced lipid perox idation in rat liver mitochondria as assessed by the formation of thio barbituric acid reactive substances (TBARS), conjugated dienes (CD) an d lipid hydroperoxides (LOOH). The effect on mitochondrial function wa s assessed by estimating the activity of succinate dehydrogenase (SDH) . The peroxidation induced was observed to be time- and concentration- dependent. Analysis of product formation and selective inhibition by scavengers of reactive oxygen species showed that the oxidative damage observed was mainly due to singlet oxygen (O-1(2)) and partly due to other reactive species. T4CPP plus light also caused significant lipid peroxidation in Sarcoma 180 ascites tumour mitochondria. Our studies indicate that T4CPP has the potential to photoinduce damage in hepatic and ascites mitochondria, a crucial site of damage in PDT.