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

Transport and accumulation of copper benzochlorin iminium salt (CDS1), a cationic photosensitizing agent, were examined using the P388/ADR m urine leukemia, which exhibits the MDR (multidrug resistance) phenotyp e, and the wild-type parent cell line, P388. The recent availability o f radioactive CDS1 permitted kinetic studies at drug levels in the sub micromolar range. Exclusion of CDS1 by P388/ADR cells could be demonst rated, indicating that this agent is a substrate for the outward trans port system associated with MDR. These results have implications with regard to the efficacy of cationic photosensitizers against this commo n neoplastic phenotype. The CDS1 was readily accumulated by P388 cells and by P388/ADR cells when the outward transport system was inhibited . Under these conditions, CDS1 was tightly bound and could not be wash ed out even when the outward transport system was reactivated.