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 murine leukemia, which exhibits the MDR (multidrug resistance) phenotype, and the wild-type parent cell line, P388. The recent availability of radioactive CDS1 permitted kinetic studies at drug levels in the submicromolar range. Exclusion of CDS1 by P388/ADR 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 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 washed out even when the outward transport system was reactivated.
Kessel
D
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Woodburn
K
K
Skalkos
D
D
D000818:Animals; D002412:Cations; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D003905:Deuteroporphyrins / Q000493:pharmacokinetics*; D004351:Drug Resistance; D007097:Imines / Q000493:pharmacokinetics*; D051379:Mice; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured
D002412:Cations; D003905:Deuteroporphyrins; D007097:Imines; D017319:Photosensitizing Agents; C081504:copper benzochlorin; D003630:Daunorubicin