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

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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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.
Research Organization:
Massachusetts Institute of Technology, Cambridge (USA)
OSTI ID:
6619198
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:5; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
ANTIPYRETICS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL ADAPTATION
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CLONING
COLCHICINE
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
DNA-CLONING
DOXORUBICIN
DRUGS
FIBROBLASTS
GENE REPRESSORS
HETEROCYCLIC COMPOUNDS
HISTONES
HYBRIDIZATION
INDOLES
ISOTOPES
LIGHT NUCLEI
MICROORGANISMS
NUCLEI
NUCLEIC ACIDS
NUCLEOPROTEINS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
PROTEINS
PYRROLES
RADIOISOTOPES
RECOMBINANT DNA
SENSITIVITY
SOMATIC CELLS
TRANSCRIPTION
VINBLASTINE
VIRUSES