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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A029
Despite the advance of cancer chemotherapy, major difficulties still need to
be overcome such as the phenomenon of cross-resistance to a variety of
natural product drugs and their synthetic derivatives. Among the different
types of drug resistance, researchers have been interested in the so-called
multidrug resistance (MDR) where P-glycoprotein (P-gp) protein is responsible
for the active efflux of the drug, out of the cell. Several cancer cell lines
have been investigated by Raman spectral imaging using red excitation. This
technique has been used to determine and quantify the intracellular
distribution of the proteins and lipids in single living sensitive and
resistant cells. Spectral images have been recorded on the 3 different single
living sensitive and resistant cells without any treatment with the drug in
the same spectral conditions. The comparison between Raman spectra in each
point, between sensitive and resistant cells, displays some changes in the
amide I intensity corresponding to the changes in the intracellular proteins
content of the cells. The spectral analysis of the sensitive and resistant
cell lines has allowed to identify the differences proper to the MDR and
non-MDR-phenotype. Cells exhibiting MDR-phenotype and obtained both by drug
selection and transfection with mdr gene, are included. Our data show that
it can be possible to identify the spectral characteristics associated with
this resistance mechanism (profile, percentage of proteins and lipids).
Resolution enhancement methods (deconvolution, derivatives, and curve
fitting) have also been used to characterise the conformational changes in
the secondary structure of cell constituents that accompany the MDR
phenotype.
RAMAN SPECTRAL IMAGING ON SINGLE LIVING CELL: A PROMISING TOOL TOWARDS CANCER
DIAGNOSIS
Beljebbar A , Morjani H, Sockalingum GD, Manfait M
Unité Médian, IFR53, UFR de Pharmacie, Université de Reims Champagne-Ardenne,
Reims CEDEX, France