Ultrastructural changes related to multidrug resistance in CEM cells: role of cytoplasmic vesicles in drug exclusion.
J Exp Ther Oncol
; 1(1): 49-61, 1996 Jan.
Article
em En
| MEDLINE
| ID: mdl-9414388
ABSTRACT
The multidrug resistance phenotype is found to be frequently associated with the overexpression of proteins which lead to a decrease of drug accumulation within human tumor cells. A 170 kDa membrane glycoprotein which is related to the overexpression of the mdr1 gene is inserted in the plasma membrane and pumps the cytotoxic drugs out of the cells. The aim of this work was to study the morphological modifications of resistant CEM/VLB 100 cells relative to their parental drug-sensitive ones and the detection of the ultrastructural localization of P-glycoprotein at the cytoplasmic level. Using a scanning electron microscope, CEM resistant cells showed wide smooth protrusions while CEM sensitive cells showed microvilli and fine folds. With transmission electron microscopy, an enhanced secretory system was observed in CEM resistant cells both electron transparent and electron opaque vesicles were associated with the Golgi system, revealed by wheat germ agglutinin-colloidal gold labelling. These vesicles were the binding site of C 219 and MRK 16 antimembrane glycoprotein antibodies, and some of them were determined to belong to the lysosomal system after PTA staining. These vesicles may be an additional way to decrease the cellular uptake of drugs in multidrug resistant cells. Moreover, some nuclear and nucleolar modifications were also observed. These observations show that MDR has wide morphological features which concern several organelles.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Leucemia Linfoide
/
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
/
Genes MDR
/
Citoplasma
Limite:
Humans
Idioma:
En
Revista:
J Exp Ther Oncol
Assunto da revista:
NEOPLASIAS
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
França