IMPAIRED ACCUMULATION OF A CATIONIC PHOTOSENSITIZING AGENT BY A CELL LINE EXHIBITING MULTIDRUG RESISTANCE

Abstract —Transport and accumulation of copper benzochlorin iminium salt (CDSl), a cationic photosensitizing agent, were examined using the P388/ADR murine leukemia, which exhibits the MDR (multidrug resistance) phe-notype, and the wild-type parent cell line, P388. The recent availability of radioactive CDSl permitted kinetic studies at drug levels in the submicromolar range. Exclusion of CDSl by P38WADR cells could be demonstrated, indicating that this agent is a substrate for the outward transport system associated with MDR. These results have implications with regard to the efficacy of cationic photosensitizers against this common neoplastic phenotype. The CDSl was readily accumulated by P388 cells and by P388/ADR cells: when the outward transport system was inhibited. Under these conditions, CDSl was tightly bound and could not be washed out even when the outward transport system was reactivated.