Abstract
Multidrug resistance can be transferred from drug-resistant LZ Chinese hamster cells to drug-susceptible mouse LTA cells by chromosome-mediated gene transfer. Analysis of genomic DNA demonstrated the transfer of multiple copies of a DNA domain which is amplified in the donor multidrug-resistant cells. The transfer of 10 to 15 copies of the Chinese hamster gene was sufficient to produce a multidrug-resistant phenotype. Chromosome transferents exhibited overexpression of an mRNA of approximately 5 kilobases which has previously been demonstrated to be encoded by the amplified DNA domain of the donor LZ cells. Phenotypic analysis of individual clones selected in adriamycin showed the resistance to be pleiotropic. All clones tested demonstrated similar levels of cross-resistance to the drugs daunorubicin and colchicine. These results indicate that the DNA sequences transferred confer the complete multidrug-resistant phenotype on recipient cells and suggest that multidrug resistance is due to overexpression of the protein encoded by the 5-kilobase mRNA.
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- Baskin F., Rosenberg R. N., Dev V. Correlation of double-minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3654–3658. doi: 10.1073/pnas.78.6.3654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Debenham P. G., Kartner N., Siminovitch L., Riordan J. R., Ling V. DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression. Mol Cell Biol. 1982 Aug;2(8):881–889. doi: 10.1128/mcb.2.8.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
- Fojo A. T., Whang-Peng J., Gottesman M. M., Pastan I. Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7661–7665. doi: 10.1073/pnas.82.22.7661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gros P., Croop J., Roninson I., Varshavsky A., Housman D. E. Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proc Natl Acad Sci U S A. 1986 Jan;83(2):337–341. doi: 10.1073/pnas.83.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grund S. H., Patil S. R., Shah H. O., Pauw P. G., Stadler J. K. Correlation of unstable multidrug cross resistance in Chinese hamster ovary cells with a homogeneously staining region on chromosome 1. Mol Cell Biol. 1983 Sep;3(9):1634–1647. doi: 10.1128/mcb.3.9.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howell N., Belli T. A., Zaczkiewicz L. T., Belli J. A. High-level, unstable adriamycin resistance in a Chinese hamster mutant cell line with double minute chromosomes. Cancer Res. 1984 Sep;44(9):4023–4029. [PubMed] [Google Scholar]
- Kartner N., Evernden-Porelle D., Bradley G., Ling V. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. 1985 Aug 29-Sep 4Nature. 316(6031):820–823. doi: 10.1038/316820a0. [DOI] [PubMed] [Google Scholar]
- Ling V., Thompson L. H. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103–116. doi: 10.1002/jcp.1040830114. [DOI] [PubMed] [Google Scholar]
- Milbrandt J. D., Azizkhan J. C., Greisen K. S., Hamlin J. L. Organization of a Chinese hamster ovary dihydrofolate reductase gene identified by phenotypic rescue. Mol Cell Biol. 1983 Jul;3(7):1266–1273. doi: 10.1128/mcb.3.7.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson D. L., Weis J. H., Przyborski M. J., Mulligan R. C., Seidman J. G., Housman D. E. Metaphase chromosome transfer of introduced selectable markers. J Mol Appl Genet. 1984;2(6):563–577. [PubMed] [Google Scholar]
- Olsen A. S., McBride O. W., Moore D. E. Number and size of human X chromosome fragments transferred to mouse cells by chromosome-mediated gene transfer. Mol Cell Biol. 1981 May;1(5):439–448. doi: 10.1128/mcb.1.5.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riordan J. R., Deuchars K., Kartner N., Alon N., Trent J., Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. 1985 Aug 29-Sep 4Nature. 316(6031):817–819. doi: 10.1038/316817a0. [DOI] [PubMed] [Google Scholar]
- Robertson S. M., Ling V., Stanners C. P. Co-amplification of double minute chromosomes, multiple drug resistance, and cell surface P-glycoprotein in DNA-mediated transformants of mouse cells. Mol Cell Biol. 1984 Mar;4(3):500–506. doi: 10.1128/mcb.4.3.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roninson I. B., Abelson H. T., Housman D. E., Howell N., Varshavsky A. Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature. 1984 Jun 14;309(5969):626–628. doi: 10.1038/309626a0. [DOI] [PubMed] [Google Scholar]
- Roninson I. B., Chin J. E., Choi K. G., Gros P., Housman D. E., Fojo A., Shen D. W., Gottesman M. M., Pastan I. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4538–4542. doi: 10.1073/pnas.83.12.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roninson I. B. Detection and mapping of homologous, repeated and amplified DNA sequences by DNA renaturation in agarose gels. Nucleic Acids Res. 1983 Aug 25;11(16):5413–5431. doi: 10.1093/nar/11.16.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schimke R. T. Gene amplification, drug resistance, and cancer. Cancer Res. 1984 May;44(5):1735–1742. [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Wahl G. M., Padgett R. A., Stark G. R. Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(phosphonacetyl)-L-aspartate-resistant hamster cells. J Biol Chem. 1979 Sep 10;254(17):8679–8689. [PubMed] [Google Scholar]