Identification of multi-drug resistant cells in sensitive Friend leukemia cells by quantitative videomicrofluorimetry.
The cellular resistance to cytotoxic drugs, particularly to anthracyclines, remains a major problem in cancer chemotherapy. A number of biochemical mechanisms have been described, one of them being a lower accumulation of drugs in resistant cells. The accumulation of Ho33342 in sensitive and resistant Friend leukemia cells was studied by quantitative fluorescence image analysis, a method which allows investigations to be made on living tissues and cells. The intensity of fluorescence is related to the amount of Ho33342 accumulated into the cells and has been found to be more intense in sensitive cells than in resistant ones. Moreover, the retention of this vital dye was inversely related to the degree of resistance in the three resistant cell lines. The addition of verapamil, which is known to reverse resistance to anthracyclines, resulted in an increase of the amount of Ho33342 accumulated in the resistant cells. Ho33342 presents a higher quantum yield than any other anthracyclines, such as adriamycin and can be used as a microfluorimetric probe to identify the resistant cells in a heterogeneous cell population.
Lahmy
S
S
Microfluorimétrie Quantitative et Pharmacocinétique Cellulaire, URA CNRS 1289, Université de Perpignan, Perpignan.
Salmon
J M
JM
Vigo
J
J
Viallet
P
P
D001562:Benzimidazoles / Q000494:pharmacology*; D004351:Drug Resistance; D005456:Fluorescent Dyes / Q000494:pharmacology; D005622:Friend murine leukemia virus; D007091:Image Processing, Computer-Assisted; D007942:Leukemia, Experimental / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D014700:Verapamil; C017807:bisbenzimide ethoxide trihydrochloride