title: Analysis of intracellular retention of morpholinyl anthracyclines in multidrug-resistant cancer-cells by interactive laser cytometry.
abstract: Interactive laser cytometry was applied to measure intracellular fluorescence of doxorubicin (DOX) accumulation in a uterine sarcoma cell line, MES-SA and a series of multidrug resistant sublines, Dx0.3, Dx1 and Dx5. Exposure of each cell line to 10 mu M DOX for 2 h resulted in an intracellular fluorescent level directly correlated to its sensitivity to the drug but inversely related to its cellular P-glycoprotein (P-gp) level. The morpholinyl anthracyclines, methoxymorpholinyl DOX (MMDX) and morpholinyl DOX (MRA), were equally highly cytotoxic against the multidrug sensitive and resistant cancer cells. After exposure to 10 mu M of MMDX or MRA for 2 h, the multidrug resistant cells, Dx5, retained as much intracellular fluorescence as the multidrug sensitive cells, MES-SA. In the resistant cells, the intracellular fluorescence of MMDX or MRA was 8 fold higher than that of DOX. Interactive laser. cytometer is a useful fool for screening cancer cells with the MDR phenotype and for identifying new anthracyclines effective against drug resistant malignancies.
authors.affiliation: STANFORD UNIV,DEPT MED,DIV ONCOL,STANFORD,CA 94305.
authors.forename: D
authors.initials: D
authors.lastname: Lau
authors.forename: G
authors.initials: G
authors.lastname: Duran
authors.forename: B
authors.initials: B
authors.lastname: Sikic