Alterations in phosphatidylcholine synthesis are associated with taxol resistance
A taxol resistant variant (J7/TAX-50) of the murine macrophage-like cell line J774.2 has been developed in vitro. The LD/sub 50/ of taxol for the resistant cells is 800-fold greater than that for the parental cell line. The J7/TAX-50 cells display phenotypic traits which are associated with multidrug resistance. J7/TAX-50 is unstably resistant and must be maintained in the presence of taxol. Cells grown in the absence of taxol for 30 days revert to drug sensitivity, and the membrane phosphoglycoprotein is lost. In contrast, the return to a normal level of drug accumulation is prolonged and requires over 8 months of growth in the absence of taxol. To characterize further the parental, resistant and revertant cell lines, the major lipids have been analyzed by 2D-chromatography and HPLC. The steady-state level of phosphatidylcholine (PC) in J7/TAX-50 is greater than in the parental or revertant cell lines. Pulse-chase studies performed with /sup 14/C-choline or /sup 32/P-orthophosphate demonstrated an increase in the turnover of PC in J7/TAX-50. Analysis by gas chromatography/mass spectrometry of the composition of the major phospholipids indicated that fatty acids attached to the sn1- and 2-positions of PC are the same in the resistant and parental cell lines. These studies suggest that an increased level of PC in the membrane may be related to drug resistance and responsible for the prolonged decrease in steady-state drug association in J7/TAX-50 grown in the absence of taxol.
- Research Organization:
- Yeshiva Univ., New York (USA)
- OSTI ID:
- 6591770
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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LABELLED COMPOUNDS
TRACER TECHNIQUES
MACROPHAGES
BIOCHEMISTRY
SENSITIVITY
PHOSPHOLIPIDS
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CHOLINE
DRUGS
GAS CHROMATOGRAPHY
IN VITRO
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
MICE
PHOSPHATES
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ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHEMISTRY
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ESTERS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PHAGOCYTES
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QUATERNARY COMPOUNDS
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RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
SPECTROSCOPY
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques