INDUCED MULTIDRUG RESISTANCE IN MURINE LEUKEMIA-L1210 AND ASSOCIATED CHANGES IN A SURFACE-MEMBRANE GLYCOPROTEIN

Autoren

Manfred Volm
Mihaly Bak
Thomas Efferth
Jürgen Mattern

DOI

10.1007/bf00391594

eISSN

1432-1335

ISSN

0171-5216

Ausgabe der Veröffentlichung

1

Zeitschrift

Journal of Cancer Research and Clinical Oncology

Sprache

en

Paginierung

17 - 24

Datum der Veröffentlichung

1989

Status

Published

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1007/bf00391594

Datum der Datenerfassung

2021

Titel

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein

Ausgabe der Zeitschrift

115

Data source: Crossref

Abstract

The aim of this study was to find out whether only resistant cells of the "multidrug-resistant" phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dnr) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabino-side-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multi-drug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210ctx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.

Addresses

German Cancer Research Center, Institute of Experimental Pathology, Heidelberg.

Autoren

M Volm
M Bak
T Efferth
T Efferth
J Mattern

DOI

10.1007/bf00391594

eISSN

1432-1335

Externe Identifier

PubMed Identifier: 2563999

Open access

false

ISSN

0171-5216

Ausgabe der Veröffentlichung

1

Zeitschrift

Journal of cancer research and clinical oncology

Schlüsselwörter

Animals
Mice
Leukemia L1210
Cyclophosphamide
Daunorubicin
Doxorubicin
Blood Proteins
Membrane Glycoproteins
Cytarabine
Antineoplastic Agents
Immunoblotting
Drug Resistance
Phenotype
Female
ATP Binding Cassette Transporter, Subfamily B, Member 1

Sprache

eng

Medium

Print

Paginierung

17 - 24

Datum der Veröffentlichung

1989

Status

Published

Datum der Datenerfassung

1989

Titel

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein.

Sub types

Journal Article

Ausgabe der Zeitschrift

115

Data source: Europe PubMed Central

Abstract

The aim of this study was to find out whether only resistant cells of the "multidrug-resistant" phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dnr) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabino-side-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multi-drug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210ctx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.

Autoren

M Volm
M Bak
T Efferth
J Mattern

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/2563999

DOI

10.1007/BF00391594

ISSN

0171-5216

Ausgabe der Veröffentlichung

1

Zeitschrift

J Cancer Res Clin Oncol

Schlüsselwörter

ATP Binding Cassette Transporter, Subfamily B, Member 1
Animals
Antineoplastic Agents
Blood Proteins
Cyclophosphamide
Cytarabine
Daunorubicin
Doxorubicin
Drug Resistance
Female
Immunoblotting
Leukemia L1210
Membrane Glycoproteins
Mice
Phenotype

Sprache

eng

Country

Germany

Paginierung

17 - 24

Datum der Veröffentlichung

1989

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

1989

Titel

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein.

Sub types

Journal Article

Ausgabe der Zeitschrift

115

Data source: PubMed

INDUCED MULTIDRUG RESISTANCE IN MURINE LEUKEMIA-L1210 AND ASSOCIATED CHANGES IN A SURFACE-MEMBRANE GLYCOPROTEIN

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