Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection
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), Vol. 85:5
- Country of Publication:
- United States
- Language:
- English
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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