EFFECTS OF PHOTOFRIN(R) PHOTODYNAMIC-ACTION ON MITOCHONDRIAL RESPIRATION AND SUPEROXIDE RADICAL GENERATION

Cyanide-resistant respiration increases after irradiation of isolated mitochondria in the presence of Photofrin(R). This suggests an enhance ment of electron leakage which has been evaluated by measuring superox ide radical formation in submitochondrial particles incubated with 6 m u g/ml Photofrin(R) in the medium and irradiated with increasing doses of light at 365 nm. After a dose of 4.5 kJ/m(2) has been delivered, s uperoxide generation Increases by a factor of similar to 2.5 at the le vel of NADH dehydrogenase and by a factor similar to 1.5 in the cyt bc (1) region. These effects have been compared with changes observed in NADH-, succinate- and ascorbate-driven respiration and their implicati ons discussed.