Expression of a Human Complementary DNA for the Multidrug Resistance Gene in Murine Hematopoietic Precursor Cells With the Use of Retroviral Gene Transfer

In multidrug resistance, cells become simultaneously resistant to anthracyclines, vinca alkaloids, epipodophyllotoxins, and certain other natural product cytotoxic drugs. Resistance results from synthesis of a multidrug transporter (P-glycoprotein) encoded by the MDR1 gene (also known as the PGY1 ge...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1990-08, Vol.82 (15), p.1260-1263
Main Authors: McLachlin, Jeanne R., Eglitis, Martin A., Ueda, Kazumitsu, Kantoff, Philip W., Pastan, Ira H., Anderson, W. French, Gottesman, Michael M.
Format: Article
Language:English
Subjects:
Animals
Bone Marrow - physiology
Bone Marrow Cells
Cells, Cultured
Clone Cells - physiology
Colchicine - pharmacology
DNA - genetics
Drug Resistance - genetics
Gene Expression - physiology
Genes, Viral - physiology
Harvey murine sarcoma virus - genetics
Hematopoietic Stem Cells - physiology
Humans
Methylcellulose
Mice
Phenotype
Retroviridae - genetics
Transcription, Genetic - physiology
Transduction, Genetic - physiology
Transfection - genetics
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Summary:In multidrug resistance, cells become simultaneously resistant to anthracyclines, vinca alkaloids, epipodophyllotoxins, and certain other natural product cytotoxic drugs. Resistance results from synthesis of a multidrug transporter (P-glycoprotein) encoded by the MDR1 gene (also known as the PGY1 gene). In the present study, a retrovirus vector containing a complementary DNA for the human multidrug resistance gene HaMDRl/A was used to transfer the multidrug resistance phenotype to bone marrow cells of the DBA/2J mouse. A high proportion of transduced bone marrow cells showed resistance to both colchicine and vinblastine, as determined by in vitro colony formation of hematopoietic precursor cells. In addition, brief culturing of the cells in a cytotoxic drug following exposure to the retrovirus vector could be used to increase the proportion of bone marrow cell colonies that were resistant. These results may serve as a model for the generation and selection of bone marrow cells resistant to the toxic effects of chemotherapeutic agents in vivo. [J Natl Cancer Inst 82: 1260–1263, 1990]
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/82.15.1260