Meso-substituted cationic porphyrins interact with dsDNA and exhibit different localization patterns in...

Meso-substituted cationic porphyrins were examined for binding dsDNA. Subcellular localization time studies used Confocal Laser Scanning Microscopy of radiation-induced fibrosarcoma (RIF) cells incubated with porphyrins. Binding studies revealed a reversible interaction between porphyrin and dsDNA that is a function of DNA shape. Binding was inhibited at high salt concentrations, and enhanced by heat and DNA denaturants such as dimethyl formamide (DMF). Trans dicationic porphyrin required more stringent binding conditions than cis dicationic and tetracationic porphyrins. Phenol extraction of porphyrin from the DNA-porphyrin complex demonstrates that cationic porphyrins do not damage dsDNA at high concentrations. Localization studies within a 24-hour range reveal different distribution patterns. Metal chelates of tetracationic porphyrin exhibited a cytoplasmic localization with the exception of the zinc chelate. Localization of other metal chelates appears to be redistributed to lysosomes and mitochondria between 3 and 6 hours post-incubation. HPPH used in PDT clinical trials localizes to the cytoplasmic compartment.