ENHANCEMENT OF NILE BLUE DERIVATIVE-INDUCED PHOTOCYTOTOXICITY BY NIGERICIN AND LOW CYTOPLASMIC PH

The mechanism of photocytotoxicity mediated by a lysosomotropic photos ensitizer, Nile blue derivative (NBS-6I), in relation to lysosome dest ruction was examined by lowering the intracellular pH with low extrace llular pH and an ionophore, nigericin. The treatment performed after p hotoirradiation had minimal effect on the cytotoxicity. However, when the treatment was initiated before photoirradiation, it caused a three orders of magnitude enhancement on cytotoxicity with a two orders of magnitude enhancement by nigericin alone. This effect on cytotoxicity resembles closely that observed on photosensitization mediated by chlo roaluminum phthalocyanine. The enhancement in this case has been attri buted to the synergistic interaction between photodamage and perturbat ion of ion transports across mitochondrial or plasma membranes by nige ricin. Because these are not the main sites of localization for Nile b lue photosensitizers nor their initial targets of photocytotoxic actio n, data from the present study suggest the possibility of an intracell ular dye translocation induced by nigericin, which redistributes the N ile blue photosensitizer from lysosomes to other sites, as a possible cause of the enhancement of cytotoxicity.