LIPID-PEROXIDATION INDUCED BY RAKIS[3,4-BIS(CARBOXYMETHYLENEOXY)PHENYL]PROPHYRIN ON PHOTOSENSITIZATION IN HEPATIC AND TUMOR MICROSOMES

The ability of a novel porphyrin, rakis[3,4-bis(carboxymethyleneoxy)ph enyl]porphyrin (T3,4-CPP), to induce photodamage in subcellular membra nes, in the form of rat hepatic and tumor microsomes, was evaluated wi th a view to locating suitable porphyrin derivative for possible use i n photodynamic therapy. This water-soluble porphyrin, on exposure to v isible light, induced a significant extent of membrane lipid peroxidat ion as assessed by the formation of thiobarbituric acid reactive subst ances, lipid hydroperoxides and conjugated dienes. The peroxidation in duced in hepatic microsomes is both time-and concentration-dependent. Using inhibitors of reactive oxygen species and comparing products of peroxidation, it is shown that the damage induced is mainly due to sin glet oxygen and partly due to other species like free radicals. T3,4-C PP also caused the generation of singlet oxygen as a function of illum ination time. Since membrane damage induced by a sensitizer on photoex citation has been considered to be an important mechanism by which pho todynamic cell killing of tumor occurs, the studies on this novel porp hyrin indicate the possible potential of this compound in photodynamic therapy. (C) 1997 Elsevier Science Ireland Ltd.