Origin of multidrug resistance in cells with and without multidrug resistance genes: Chromosome reassortments catalyzed by aneuploidy
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Cancer cells and aneuploid cell lines can acquire resistance against multiple unrelated chemotherapeutic drugs that are over 3,000-fold those of normal levels and display spontaneous resistances up to 20-fold of normal levels. Two different mechanisms were proposed for this phenotype: (i) classical mutation of drug metabolizing genes or (ii) chromosome reassortments, catalyzed by cancer- and cell line-specific aneuploidy, which generate, via new gene dosage combinations, a plethora of cancer phenotypes, including drug resistance. To distinguish between these mechanisms, we have asked whether three mouse cell lines can become drug resistant, from which two or three genes have been deleted, and on which multidrug resistance is thought to depend: Mdr1a, Mdr1b, and Mrp1. Because all three lines could acquire multidrug resistance and were aneuploid, whereas diploid mouse cells could not, we conclude that aneuploid cells become drug resistant via specific chromosome assortments, independent of putative resistance genes. We have asked further whether aneuploid drug-resistant Chinese hamster cells revert spontaneously to drug sensitivity in the absence of cytotoxic drugs at the high rates that are typical of chromosome reassortments catalyzed by aneuploidy or at the very low or zero rates (i.e., deletion) of gene mutation. We found that four drug-resistant hamster cell lines reverted to drug sensitivity at rates of about 2-3% per generation, whereas two closely related lines remained resistant under our conditions. Thus, the karyotypic instability generated by aneuploidy emerges as the common source of the various levels of drug resistance of cancer cells: minor spontaneous resistances reflect accidental chromosome assortments, the high selected resistances reflect complex specific assortments, and multidrug resistance reflects new combinations of unselected genes located on the same chromosomes as selected genes.
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Large genomic rearrangements such as aneuploidies result in the concerted over- or under-expression of several genes.
“large genomic re-arrangements such as aneuploidies are good candidates because they result in the concerted over- or under-expression (depending on whether there is a gain or loss of chromosomes) of several genes”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [124]
Aneuploidies are rather common, particularly under stress conditions.
“they are rather common, particularly under stress conditions [124,125,126]”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [124]
Aneuploidies are well tolerated by cells.
“they are well tolerated by the cells”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [124]
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Cites
Cancer: Principles and Practice of Oncology.
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-819_4 · Cited by 8,524 · see citing works
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001) · Science · doi:10.1126/science.1062538 · Cited by 3,104 · see citing works
Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037 · see citing works
Genetic instability in colorectal cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1997) · Nature · doi:10.1038/386623a0 · Cited by 1,995 · see citing works
Cancer: Principles and Practice of Oncology
Gunn, W. G. (1994) · JAMA · doi:10.1001/jama.1994.03510350091047 · Cited by 1,810 · see citing works
The chromosomes in human cancer and leukemia
Sandberg, A. A. (1990) · Medical Entomology and Zoology · Cited by 1,763 · see citing works
A family of drug transporters: the multidrug resistance-associated proteins
Borst, P., Evers, R., Kool, M., & Wijnholds, J. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.16.1295 · Cited by 1,751 · see citing works
Cell Surface P-Glycoprotein Associated with Multidrug Resistance in Mammalian Cell Lines
Kartner, N., Riordan, J. R., & Ling, V. W. T. (1983) · Science · doi:10.1126/science.6137059 · Cited by 1,005 · see citing works
Human Genetics. Problems and Approaches.
(1980) · Annals of Internal Medicine · doi:10.7326/0003-4819-93-1-163_3 · Cited by 991 · see citing works
Biedler, J. L., & Riehm, H. (1970) · PubMed · Cited by 748 · see citing works
Cui, Y., König, J., Buchholz, U., Spring, H., Leier, I., & KEPPLER, D. O. R. (1999) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23190-4 · Cited by 674 · see citing works
Scheper, R. J., Broxterman, H. J., Scheffer, G. L., Kaaijk, P., Dalton, W. S., van Heijningen, T. H. M., van Kalken, C. K., Slovak, M. L., de Vries, E. G. E., & van der Valk, P. (1993) · PubMed · Cited by 493 · see citing works
On the nature of hereditable variation in cultured somatic cells
Siminovitch, L. (1976) · Cell · doi:10.1016/0092-8674(76)90249-x · Cited by 485 · see citing works
Trock, B. J., Leonessa, F., & Clarke, R. C. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.13.917 · Cited by 434 · see citing works
Bargou, R. C., Jürchott, K., Wagener, C., Bergmann, S., Metzner, S., Bommert, K., Mapara, M. Y., Winzer, K., Dietel, M., Dörken, B., et al. (1997) · Nature Medicine · doi:10.1038/nm0497-447 · Cited by 423 · see citing works
Structural, mechanistic and clinical aspects of MRP1
Hipfner, D. R., Deeley, R. G., & Cole, S. P. C. (1999) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(99)00168-6 · Cited by 412 · see citing works
Vogel, F., & Motulsky, A. G. (1986) · Springer eBooks · doi:10.1007/978-3-662-02489-8 · Cited by 393 · see citing works
Genetic instability of cancer cells is proportional to their degree of aneuploidy
DUESBERG, P. H., Rausch, C., Rasnick, D., & Hehlmann, R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13692 · Cited by 376 · see citing works
Self-citationLi, R., Sonik, A., Stindl, R., Rasnick, D., & DUESBERG, P. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3236 · Cited by 258 · see citing works
Self-citationAneuploidy, the somatic mutation that makes cancer a species of its own
DUESBERG, P. H., & Rasnick, D. (2000) · Cell Motility and the Cytoskeleton · doi:10.1002/1097-0169(200010)47:2 · Cited by 229 · see citing works
Self-citationlzquierdo, M. A., Zee, A. G. V. D., Vermorken, J. B., van der Valk, P., Beliën, J. A. M., Giaccone, G., Scheffer, G. L., Flens, M. J., Pinedo, H. M., Kenemans, P., et al. (1995) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/87.16.1230 · Cited by 220 · see citing works
ROLE OF CHROMOSOMES IN CANCEROGENESIS, AS STUDIED IN SERIAL TISSUE CULTURE OF MAMMALIAN CELLS
LEVAN, A., & Biesele, J. J. (1958) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1958.tb54666.x · Cited by 219 · see citing works
Aneuploidy: Etiology and mechanisms
(1987) · Gene · doi:10.1016/0378-1119(87)90063-1 · Cited by 201 · see citing works
Chromosome abnormalities in human reproductive wastage
Hassold, T. J. (1986) · Trends in Genetics · doi:10.1016/0168-9525(86)90194-0 · Cited by 201 · see citing works
Allen, J. D., Brinkhuis, R. F., van Deemter, L., Wijnholds, J., & Schinkel, A. H. (2000) · PubMed · Cited by 200 · see citing works
Aneuploidy and ageing: chromosome studies on a random sample of the population using G-banding
Galloway, S. M., & BUCKTON, K. E. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000130842 · Cited by 195 · see citing works
ANEUPLOIDY IN THE DEGENERATIVE PHASE OF SERIAL CULTIVATION OF HUMAN CELL STRAINS
SAKSELA, E., & Moorhead, P. S. (1963) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.50.2.390 · Cited by 192 · see citing works
Foundations of experimental embryology
Willier, B. H., & OPPENHEIMER, J. M. (1964) · Medical Entomology and Zoology · Cited by 185 · see citing works
van der Zee, A. G. J., Hollema, H., Suurmeijer, A. J. H., Krans, M., Sluiter, W. J., Willemse, P. H. B., Aalders, J. G., & de Vries, E. G. E. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.1.70 · Cited by 184 · see citing works
Pitot, H. C. (1981) · Medical Entomology and Zoology · Cited by 179 · see citing works
The chromosomes in ontogeny and oncogeny.
Hauschka, T. S. (1961) · PubMed · Cited by 175 · see citing works
ROLE OF CHROMOSOMES IN CANCEROGENESIS, AS STUDIED IN SERIAL TISSUE CULTURE OF MAMMALIAN CELLS
LEVAN, A., & Biesele, J. J. (1958) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1958.tb46820.x · Cited by 175 · see citing works
Mutation rates in cells at different ploidy levels
Harris, M. (1971) · Journal of Cellular Physiology · doi:10.1002/jcp.1040780204 · Cited by 172 · see citing works
Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells
Li, R., Yerganian, G., DUESBERG, P. H., Kraemer, A., Willer, A., Rausch, C., & Hehlmann, R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14506 · Cited by 172 · see citing works
Self-citationDUESBERG, P. H., Stindl, R., & Hehlmann, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14295 · Cited by 168 · see citing works
Self-citationYoung, L. C., Campling, B. G., Voskoglou-Nomikos, T., Cole, S. P. C., Deeley, R. G., & Gerlach, J. H. (1999) · PubMed · Cited by 168 · see citing works
How aneuploidy affects metabolic control and causes cancer
Rasnick, D., & DUESBERG, P. H. (1999) · Biochemical Journal · doi:10.1042/bj3400621 · Cited by 164 · see citing works
Self-citationThe Cellular Basis of Tumor Progression
Heppner, G. H., & Miller, F. R. (1997) · International review of cytology · doi:10.1016/s0074-7696(08)62230-5 · Cited by 161 · see citing works
Studies on thymidine kinase in cultured mouse fibroblasts
Littlefield, J. W. (1965) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(65)90206-6 · Cited by 160 · see citing works
Mickisch, G., Merlino, G. T., Galski, H., et al. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.2.547 · Cited by 148 · see citing works
Chu, E. H. Y., Brimer, P. A., Jacobson, K. B., et al. (1969) · Genetics · doi:10.1093/genetics/62.2.359 · Cited by 146 · see citing works
Metastatic variants are generated spontaneously at a high rate in mouse KHT tumor.
Harris, J. F., Chambers, A. F., Hill, R. P., & Ling, V. W. T. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.18.5547 · Cited by 137 · see citing works
Mutations affecting adenine phosphoribosyl transferase activity in Chinese hamster cells
Chasin, L. A. (1974) · Cell · doi:10.1016/0092-8674(74)90006-3 · Cited by 131 · see citing works
Mutants of cultured chinese hamster cells deficient in adenine phosphoribosyl transferase
Jones, G. E., & Sargent, P. A. (1974) · Cell · doi:10.1016/0092-8674(74)90007-5 · Cited by 127 · see citing works
Origin of the Resistance of Leukæmic Cells to Folic Acid Antagonists
Law, L. W. (1952) · Nature · doi:10.1038/169628a0 · Cited by 115 · see citing works
Isolation and characterization of thymidine transport mutants of Chinese hamster cells
Breslow, R., & Goldsby, R. A. (1969) · Experimental Cell Research · doi:10.1016/0014-4827(69)90567-9 · Cited by 106 · see citing works
Mechanisms of drug resistance in ovarian cancer
Johnson, S. W., Ozols, R. F., & Hamilton, T. C. (2010) · Cancer · doi:10.1002/cncr.2820710224 · Cited by 98 · see citing works
Effect of Ploidy and Mutagens on Bromodeoxyuridine Resistance in Haploid and Diploid Frog Cells
Mezger‐Freed, L. (1972) · Nature New Biology · doi:10.1038/newbio235245a0 · Cited by 95 · see citing works
Hook, E. B. (1985) · Springer eBooks · doi:10.1007/978-1-4613-2127-9_2 · Cited by 89 · see citing works
Inverse relationship between chromosome ploidy and host-specificity of sixteen transplantable tumors
Hauschka, T. S., & LEVAN, A. (1953) · Experimental Cell Research · doi:10.1016/0014-4827(53)90171-2 · Cited by 87 · see citing works
Veneroni, S., Zaffaroni, N., Daidone, M. G., et al. (1994) · European Journal of Cancer · doi:10.1016/0959-8049(94)90132-5 · Cited by 81 · see citing works
Carr, D. T. (1986) · JAMA · doi:10.1001/jama.1986.03380130135048 · Cited by 76 · see citing works
The effects of chemotherapy on the kinetics of leukemic cell behavior.
Skipper, H. E. (1965) · PubMed · Cited by 75 · see citing works
McCormick, F. P. (2001) · Nature · doi:10.1038/35085665 · Cited by 72 · see citing works
Franks, L. M. (1976) · Nature · doi:10.1038/259429c0 · Cited by 69 · see citing works
The cells of the body: a history of somatic cell genetics
Horder, T. J. (1996) · Choice Reviews Online · doi:10.5860/choice.33-4485 · Cited by 62 · see citing works
Biochemically marked variants of the syrian hamster fibroblast cell line BHK21 and its derivatives
Subak-Sharpe, H. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90432-5 · Cited by 60 · see citing works
Cytogenetically marked clones in human fibroblasts cultured from normal subjects
Harnden, D. G., BENN, P. A., Oxford, J. M., Taylor, A. M. R., & Webb, T. (1976) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01539242 · Cited by 58 · see citing works
Rappa, G., Finch, R. A., Sartorelli, A. C., et al. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00074-x · Cited by 55 · see citing works
Are Centrosomes or Aneuploidy the Key to Cancer?
DUESBERG, P. H. (1999) · Science · doi:10.1126/science.284.5423.2089f · Cited by 51 · see citing works
Self-citationPolyploidy--More Is More or Less
Hieter, P., & Griffiths, T. (1999) · Science · doi:10.1126/science.285.5425.210 · Cited by 50 · see citing works
Correlation of chromosomal and physiologic changes in tumors
Hauschka, T. S. (1958) · Journal of Cellular and Comparative Physiology · doi:10.1002/jcp.1030520411 · Cited by 47 · see citing works
ISOLATION AND STUDY OF MUTANTS FROM MAMMALIAN CELLS IN CULTURE
Lieberman, I., & Ove, P. (1959) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.45.6.867 · Cited by 45 · see citing works
A STUDY OF THE RELATIONSHIP BETWEEN KARYOTYPE AND PHENOTYPE IN CLONES LINES OF STRAIN HeLa
Vogt, M. (1959) · Genetics · doi:10.1093/genetics/44.6.1257 · Cited by 44 · see citing works
P glycoprotein (P-gp) and drug resistance – time for reappraisal?
Kaye, S. B. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.119 · Cited by 44 · see citing works
Mutagenesis to aminopterin resistance in cultured hamster cells
Orkin, S. H., & Littlefield, J. W. (1971) · Experimental Cell Research · doi:10.1016/0014-4827(71)90322-3 · Cited by 37 · see citing works
Chromosomal Variation and the Origin of Drug-Resistant Mutants in Mammalian Cell Lines
Terzi, M. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.12.5027 · Cited by 37 · see citing works
Karyotype evolution and tumor development
YOSIDA, T. H. (1983) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(83)90047-x · Cited by 32 · see citing works
Genetics of mammalian cell cultures
Gartler, S. M., & Pious, D. A. (1966) · Human Genetics · doi:10.1007/bf00291512 · Cited by 32 · see citing works
Biedler, J. L., Albrecht, A., & Hutchison, D. J. (1965) · PubMed · Cited by 31 · see citing works
Diagnostic and prognostic value of DNA cytometry in gynecologic cytology.
Böcking, A., & Chatelain, R. (1989) · PubMed · Cited by 30 · see citing works
Chromosomal constitution and amethopterin resistance in cultured mouse cells.
Hakala, M. T., & Ishihara, T. (1962) · PubMed · Cited by 29 · see citing works
Genomic Imbalances Associated with Acquired Resistance to Platinum Analogues
Leyland-Jones, B. R., Kèlland, L. R., Harrap, K. R., & Hiorns, L. R. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65102-4 · Cited by 28 · see citing works
Chiu, D. T. W., & DUESBERG, P. H. (1995) · Genetica · doi:10.1007/bf01435004 · Cited by 27 · see citing works
Self-citationMolecular cytogenetics of multiple drug resistance
Schoenlein, P. V. (1993) · Cytotechnology · doi:10.1007/bf00744658 · Cited by 27 · see citing works
Therman, E. (1986) · Springer eBooks · doi:10.1007/978-1-4684-0269-8 · Cited by 26 · see citing works
A genetic change in a tissue culture line of neoplastic cells
Vogt, M. (1958) · Journal of Cellular and Comparative Physiology · doi:10.1002/jcp.1030520413 · Cited by 24 · see citing works
Cisplatin-DNA damage recognition proteins in human tumour extracts
Bissett, D., McLaughlin, K., Kelland, L., et al. (1993) · British Journal of Cancer · doi:10.1038/bjc.1993.135 · Cited by 23 · see citing works
Peterson, A. R., Peterson, H., & Heidelberger, C. (1975) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(75)90026-3 · Cited by 23 · see citing works
Nonrandom de novo chromosome aberrations in human lymphocytes and amniotic cells
Petersson, H., & Mitelman, F. (2008) · Hereditas · doi:10.1111/j.1601-5223.1985.tb00462.x · Cited by 21 · see citing works
Drug resistance: still on the learning curve.
Bates, S. E. (1999) · PubMed · Cited by 20 · see citing works
Tew, K. D., Moy, B. C., & Hartley‐Asp, B. (1983) · Experimental Cell Research · doi:10.1016/0014-4827(83)90356-7 · Cited by 19 · see citing works
Tumorigenicity of Tissue Culture Cells
McAllister, R. M., & Coriell, L. L. (1959) · Cancer Research · Cited by 14 · see citing works
When Theories Collide: Experts Develop Different Models for Carcinogenesis
Webb, T. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.2.92 · Cited by 13 · see citing works
Indian state plans compulsory HIV testing, segregation and branding
Jayaraman, K. S. (1998) · Nature Medicine · doi:10.1038/nm0498-378a · Cited by 12 · see citing works
How the Biosphere is Organized
May, R. M. (1999) · Science · doi:10.1126/science.286.5447.2091 · Cited by 8 · see citing works
Gibbs, W. W. (2001) · Scientific American · doi:10.1038/scientificamerican0801-30 · Cited by 3 · see citing works
Doyle, R. (2001) · Scientific American · doi:10.1038/scientificamerican0701-30 · Cited by 2 · see citing works
In a dry land. The southwest faces a dry future, but there are ways to cope.
Doyle, R. (2001) · PubMed · Cited by 2 · see citing works
All in the mind. Fact or artifact? The placebo effect may be a little of both.
Ww, G. (2001) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 21
- [2]Skipper H E. Cancer Res. 1965;25:1544–1550. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/5861078/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=H%20E%20Skipper&volume=25&publication_year=1965&pages=1544-1550&pmid=5861078&)]
- [11]Biedler J L, Riehm H. Cancer Res. 1970;30:1174–1184. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/5533992/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=J%20L%20Biedler&author=H%20Riehm&volume=30&publication_year=1970&pages=1174-1184&pmid=5533992&)]
- [13]Cui Y, Konig J, Buchholz J K, Spring H, Leier I, Keppler D. Mol Pharmacol. 1999;55:929–937. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10220572/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Mol%20Pharmacol&author=Y%20Cui&author=J%20Konig&author=J%20K%20Buchholz&author=H%20Spring&author=I%20Leier&volume=55&publication_year=1999&pages=929-937&pmid=10220572&)]
- [16]Allen J D, Brinkhuis R F, van Deemter L, Wijnholds J, Schinkel A H. Cancer Res. 2000;60:5761–5766. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11059771/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=J%20D%20Allen&author=R%20F%20Brinkhuis&author=L%20van%20Deemter&author=J%20Wijnholds&author=A%20H%20Schinkel&volume=60&publication_year=2000&pages=5761-5766&pmid=11059771&)]
- [17]McAllister R M, Corriell L L. Cancer Res. 1959;19:1040–1044. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=R%20M%20McAllister&author=L%20L%20Corriell&volume=19&publication_year=1959&pages=1040-1044&)]
- [20]Lewin B. Genes V. Oxford, U.K.: Oxford Univ. Press; 1994. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Genes%20V&author=B%20Lewin&publication_year=1994&)]
- [24]Gartler S M, Pious D E. Humangenetik. 1966;2:83–114. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Humangenetik&author=S%20M%20Gartler&author=D%20E%20Pious&volume=2&publication_year=1966&pages=83-114&)]
- [30]Bates S E. Clin Cancer Res. 1999;5:3346–3348. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10589742/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Clin%20Cancer%20Res&author=S%20E%20Bates&volume=5&publication_year=1999&pages=3346-3348&pmid=10589742&)]
- [31]Scheper R J, Broxterman H J, Scheffer G L, Kaaijk P, Dalton W S, van Heijningen T H, van Kalken C K, Slovak M L, de Vries E G, van der Valk P, et al. Cancer Res. 1993;53:1475–1479. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/7680954/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=R%20J%20Scheper&author=H%20J%20Broxterman&author=G%20L%20Scheffer&author=P%20Kaaijk&author=W%20S%20Dalton&volume=53&publication_year=1993&pages=1475-1479&pmid=7680954&)]
- [34]Young L C, Campling B G, Voskoglou-Nomikos T, Cole S P, Deeley R G, Gerlach J H. Clin Cancer Res. 1999;5:673–680. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10100721/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Clin%20Cancer%20Res&author=L%20C%20Young&author=B%20G%20Campling&author=T%20Voskoglou-Nomikos&author=S%20P%20Cole&author=R%20G%20Deeley&volume=5&publication_year=1999&pages=673-680&pmid=10100721&)]
- [40]Hassold T J. Trends Genet. 1986;2:105–110. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Trends%20Genet&author=T%20J%20Hassold&volume=2&publication_year=1986&pages=105-110&)]
- [41]Heim S, Mitelman F. Cancer Cytogenet. New York: Wiley–Liss; 1995. [[Google Scholar](https://scholar.google.com/scholar_lookup?title=Cancer%20Cytogenet.&author=S%20Heim&author=F%20Mitelman&publication_year=1995&)]
- [50]Bocking A, Chatelain R. Anal Quant Cytol Histol. 1989;11:177–186. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/2663008/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Anal%20Quant%20Cytol%20Histol&author=A%20Bocking&author=R%20Chatelain&volume=11&publication_year=1989&pages=177-186&pmid=2663008&)]
- [53]Rasnick D, Duesberg P. Biochem J. 1999;340:621–630. [[PMC free article](/articles/PMC1220292/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10359645/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Biochem%20J&author=D%20Rasnick&author=P%20Duesberg&volume=340&publication_year=1999&pages=621-630&pmid=10359645&)]
- [54]Li R, Sonik A, Stindl R, Rasnick D, Duesberg P. Proc Natl Acad Sci USA. 2000;97:3236–3241. doi: 10.1073/pnas.040529797. . (First Published March 21, 2000; 10.1073/pnas.040529797) [[DOI](https://doi.org/10.1073/pnas.040529797)] [[PMC free article](/articles/PMC16222/)] [[PubMed](https://pubmed.ncbi.nlm.nih.gov/10725343/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Proc%20Natl%20Acad%20Sci%20USA&author=R%20Li&author=A%20Sonik&author=R%20Stindl&author=D%20Rasnick&author=P%20Duesberg&volume=97&publication_year=2000&pages=3236-3241&pmid=10725343&doi=10.1073/pnas.040529797&)] · DOI
- [56]Hauschka T S, Levan A. Exp Cell Res. 1953;4:457–467. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Exp%20Cell%20Res&author=T%20S%20Hauschka&author=A%20Levan&volume=4&publication_year=1953&pages=457-467&)]
- [57]Hauschka T S. Cancer Res. 1961;21:957–981. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/13712320/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=T%20S%20Hauschka&volume=21&publication_year=1961&pages=957-981&pmid=13712320&)]
- [58]Vogt M. J Cell Comp Physiol. 1958;52(Suppl.):271–285. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Cell%20Comp%20Physiol&author=M%20Vogt&volume=52(Suppl.)&publication_year=1958&pages=271-285&)]
- [69]Hakala M T, Ishihara T. Cancer Res. 1962;22:987–992. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/13952013/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=M%20T%20Hakala&author=T%20Ishihara&volume=22&publication_year=1962&pages=987-992&pmid=13952013&)]
- [70]Biedler J L, Albrecht A M, Hutchison D J. Cancer Res. 1965;25:246–257. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/14264058/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Cancer%20Res&author=J%20L%20Biedler&author=A%20M%20Albrecht&author=D%20J%20Hutchison&volume=25&publication_year=1965&pages=246-257&pmid=14264058&)]
- [79]Gibbs W W. Sci Am. 2001;285:30–32. [[PubMed](https://pubmed.ncbi.nlm.nih.gov/11589196/)] [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Sci%20Am&author=W%20W%20Gibbs&volume=285&publication_year=2001&pages=30-32&pmid=11589196&)]
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- Authors
- Duesberg, P., Stindl, R., & Hehlmann, R.
- Affiliations
- Heidelberg University (DE)
- Department of Molecular and Cell Biology, Stanley Hall, University of California, Berkeley, CA 94720; and III Medizinische Klinik Mannheim of the University of Heidelberg, Wiesbadener Strasse7-11, 68305 Mannheim, Germany
- ORCID
- Stindl, Reinhard
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-09-11
- Volume
- 98
- Issue
- 20
- Pages
- 11283-11288
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC58721
- OpenAlex
- W1979499502
- Cited by
- 106
- References
- 90
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 4
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- multidrug resistance, aneuploidy, karyotypic instability, mdr1a, mdr1b, MRP1, drug resistance genes, gene dosage, mouse cell lines, Chinese hamster cells, cancer chemotherapy resistance
- MeSH terms
- ATP-Binding Cassette Sub-Family B Member 4, Aneuploidy, Animals, Cell Line, Cell Survival, Chromosomes, Cytarabine, Cytotoxins, Dactinomycin, Demecolcine, Embryo, Mammalian, Cricetinae, Methotrexate, Puromycin, Transfection, CHO Cells, Drug Resistance, Multiple, ATP Binding Cassette Transporter, Subfamily B, ATP-Binding Cassette Transporters, Multidrug Resistance-Associated Proteins, ATP-Binding Cassette, Sub-Family C Proteins, Mice
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