title: Cellular daunomycin fluorescence in multidrug resistant 2780AD cells and its relation to cellular drug localisation.
abstract: Multidrug resistant (MDR) 2780AD human ovarian carcinoma cells were loaded with the fluorescent anticancer agent daunomycin (DN). Fluorescence anisotropy was lower than for corresponding A2780 wild-type cells, indicating that DN was less rigidly bound than in the wild-type cells. Average fluorescence quenching of DN was lower for 2780AD cells. Data were fitted into a model with a highly quenched fraction (fraction A), corresponding to DN intercalated in DNA, and an unquenched fraction (fraction B). The ratio A/B was one order of magnitude lower for the MDR cells than for the wild-type cells. Two other MDR cell lines were investigated and low A/B ratios were found in both cases. Thus, evidence has been provided that in MDR cells the DNA-bound fraction is relatively low and that more free DN is present, for example in acidic vesicles.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Lankelma
authors.forename: H S
authors.initials: HS
authors.lastname: Mülder
authors.forename: F
authors.initials: F
authors.lastname: van Mourik
authors.forename: H W
authors.initials: HW
authors.lastname: Wong Fong Sang
authors.forename: R
authors.initials: R
authors.lastname: Kraayenhof
authors.forename: R
authors.initials: R
authors.lastname: van Grondelle
mesh_terms: D004273:DNA, Neoplasm / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005454:Fluorescence Polarization; D006801:Humans; D007364:Intercalating Agents; D008954:Models, Biological; D010051:Ovarian Neoplasms; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D007364:Intercalating Agents; D003630:Daunorubicin