Oxidative damage induced by a novel porphyrin in tumour mitochondria and other model systems: Potential applications in photodynamic therapy

Abstract

With a view to locate new porphyrins for use in PDT, we have evaluated the ability of a novel water soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes and nucleic acids using rat hepatic and tumour mitochondria and plasmid pBR322 DNA as model systems. T4CPP, when exposed to visible light, induced significant lipid peroxidation and enzyme inactivation in mitochondria and single strand breaks in plasmid pBR322 DNA. Analysis of the products of peroxidation and selective inhibition by specific inhibitors and effect of deuteration showed that the oxidative damage induced was mainly due to singlet oxygen (O-1(2)) and partly due to other reactive species. Copyright (C) 1997 Elsevier Science Ltd.