Porphyrin photosensitization of multi-drug resistant cell types.
The P388 murine leukemia and P388/ADR, a subline expressing the multi-drug resistance (MDR) phenotype, were examined with regard to the role of MDR as a determinant of responsiveness to photodynamic therapy in vitro. Mesoporphyrin was used as a model substrate. We found no differences in porphyrin accumulation nor transport alterations associated with exposure of P388/ADR cells to the verapamil analog DMDP. There was a significant correlation between photodamage to mitochondria vs loss of cell viability in both cell lines, and LD50 sensitizer levels were not significantly different in P388 vs P388/ADR. P388/ADR cells were partly resistant to porphyrin-catalyzed photodamage to amino acid transport, but this result was not associated with differences in sensitizer localization, as indicated by fluorescence studies. Moreover, photodamage to membrane transport was not associated with loss of viability. These studies suggest that cells which express the MDR phenotype are unlikely to be cross-resistant to photodynamic therapy.
Kessel
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Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Erickson
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C
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D004351:Drug Resistance; D008652:Mesoporphyrins / Q000378:metabolism / Q000494:pharmacology*; D010641:Phenotype; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects
D000903:Antibiotics, Antineoplastic; D008652:Mesoporphyrins; D011838:Radiation-Sensitizing Agents; C031468:mesoporphyrin IX