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Title: Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection

Abstract

The authors have constructed a retrovirus expression vector that carries the murine mdr cDNA transcribed under the control of the human H4 histone promoter to examine the feasibility of efficiently transferring a multidrug resistance phenotype to cells without requiring drug selection. This approach will facilitate the transfer of mdr cDNA to hematopoietic progenitor cells for the study of multidrug resistance in vivo. The retrovirus vector pHmdr has been used for transmission and expression of the mdr cDNA in initially drug-sensitive NIH 3T3 fibroblasts. Selection of pHmdr infectants in the cytotoxic agents colchicine or doxorubicin gave rise to highly multidrug-resistant colonies containing a single gene copy of the vector. Moreover, in the analysis of 12 cloned unselected NIH 3T3 cell infectants, a multidrug resistance phenotype was conferred by as few as two copies of the pHmdr vector. Overexpression of the mdr cDNA in drug-selected and unselected pHmdr infectants was directly related to cell survival in three cytotoxic agents tested. These results hold significant implications for the study of multidrug resistance in vivo.

Authors:
; ; ;
Publication Date:
Research Org.:
Massachusetts Institute of Technology, Cambridge (USA)
OSTI Identifier:
6619198
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. U.S.A.; (United States)
Additional Journal Information:
Journal Volume: 85:5
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANTINEOPLASTIC DRUGS; SENSITIVITY; FIBROBLASTS; BIOLOGICAL ADAPTATION; RECOMBINANT DNA; DNA-CLONING; COLCHICINE; DOXORUBICIN; GENE REPRESSORS; HISTONES; HYBRIDIZATION; PHOSPHORUS 32; PLASMIDS; TRANSCRIPTION; VINBLASTINE; VIRUSES; ALKALOIDS; ANIMAL CELLS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTIPYRETICS; AROMATICS; AZAARENES; AZOLES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM DEPRESSANTS; CLONING; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; DNA; DNA HYBRIDIZATION; DRUGS; HETEROCYCLIC COMPOUNDS; INDOLES; ISOTOPES; LIGHT NUCLEI; MICROORGANISMS; NUCLEI; NUCLEIC ACIDS; NUCLEOPROTEINS; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PARASITES; PHOSPHORUS ISOTOPES; PROTEINS; PYRROLES; RADIOISOTOPES; SOMATIC CELLS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Guild, B C, Mulligan, R C, Gros, P, and Housman, D E. Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection. United States: N. p., 1988. Web. doi:10.1073/pnas.85.5.1595.
Guild, B C, Mulligan, R C, Gros, P, & Housman, D E. Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection. United States. https://doi.org/10.1073/pnas.85.5.1595
Guild, B C, Mulligan, R C, Gros, P, and Housman, D E. 1988. "Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection". United States. https://doi.org/10.1073/pnas.85.5.1595.
@article{osti_6619198,
title = {Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection},
author = {Guild, B C and Mulligan, R C and Gros, P and Housman, D E},
abstractNote = {The authors have constructed a retrovirus expression vector that carries the murine mdr cDNA transcribed under the control of the human H4 histone promoter to examine the feasibility of efficiently transferring a multidrug resistance phenotype to cells without requiring drug selection. This approach will facilitate the transfer of mdr cDNA to hematopoietic progenitor cells for the study of multidrug resistance in vivo. The retrovirus vector pHmdr has been used for transmission and expression of the mdr cDNA in initially drug-sensitive NIH 3T3 fibroblasts. Selection of pHmdr infectants in the cytotoxic agents colchicine or doxorubicin gave rise to highly multidrug-resistant colonies containing a single gene copy of the vector. Moreover, in the analysis of 12 cloned unselected NIH 3T3 cell infectants, a multidrug resistance phenotype was conferred by as few as two copies of the pHmdr vector. Overexpression of the mdr cDNA in drug-selected and unselected pHmdr infectants was directly related to cell survival in three cytotoxic agents tested. These results hold significant implications for the study of multidrug resistance in vivo.},
doi = {10.1073/pnas.85.5.1595},
url = {https://www.osti.gov/biblio/6619198}, journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = ,
volume = 85:5,
place = {United States},
year = {Tue Mar 01 00:00:00 EST 1988},
month = {Tue Mar 01 00:00:00 EST 1988}
}