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Proceedings Paper

Plasma Membrane Lesions In Anthracycline-Resistant Tumor Cells Probed Using A Fluorescent Dye
Author(s): Thomas G. Burke; James H. Doroshow
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Paper Abstract

Human cancer cells selected for resistance to several structurally unrelated cytotoxic drugs are known to display plasma membrane alterations such as amplified levels of a variety of glycoproteins, modifications in lipid composition, alterations in membrane fluidity and increased cellular fragility to osmotic shock. We have studied the plasma membrane fluidity of HL60 human leukemia cells and MCF-7 human breast cancer cells that have been selected for acquired resistance against the cytocidal effects of the anthracycline anticancer drug Adriamycin. Fluidity measurements were accomplished by evaluating the fluorescence anisotropy of the plasma membrane specific probe trimethylamino-1,6-dipihenylhexatriene (TMA.DPH) bound to whole, living cells. TMA.DPH anisotropy values for MCF-7 sensitive and 12-fold resistant cells were 0.306 and 0.285, respectively, while anisotropy values for HL-60 sensitive and 80-fold resistant cells lines were 0.310 and 0.295, respectively. In all cases, cell viability exceeded 97% and anisotropy values were subject to a day-to-day uncertainty of ±2%. Our results demonstrate that increased plasma membrane fluidity apparently accompanies the development of resistance in both cell lines. Because it is known that increased membrane fluidity results in significantly decreased Adriamycin binding in artificial membrane systems, we propose here that decreased drug associations with fluidized, plasma membrane lipid bilayer regions may be a mechanism which contributes, in part, to the reduced rates of drug accumulation observed in HL60 and MCF-7 cells resistant to Adriamycin.

Paper Details

Date Published: 13 June 1989
PDF: 9 pages
Proc. SPIE 1063, New Technologies in Cytometry, (13 June 1989); doi: 10.1117/12.951904
Show Author Affiliations
Thomas G. Burke, City of Hope National Medical Center (United States)
James H. Doroshow, City of Hope National Medical Center (United States)

Published in SPIE Proceedings Vol. 1063:
New Technologies in Cytometry
Gary C. Salzman, Editor(s)

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