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Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes.
Open accessAbstract
Selection of mammalian cells in progressively increasing concentrations of methotrexate results in selective amplification of DNA sequences coding for dihydrofolate reductase (tetrahydrofolate dehydrogenase, 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3). In some cell variants the amplified genes are stable with growth in the absence of methotrexate, whereas in other variants the amplified genes are lost from the population. We have previously reported that in a stably amplified variant of Chinese hamster ovary cells, the genes are localized to a single chromosome. Herein we report that in mouse S-180 and L5178Y cell lines unstably amplified dihydrofolate reductase DNA sequences are associated with small, paired chromosomal elements denoted "double minute chromosomes," whereas in stably amplified cells of the same origin, the genes are associated with large chromosomes.
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Cited by
The Pharmacology and Clinical Use of Methotrexate
Jolivet, J., Cowan, K. H., Curt, G. A., Clendeninn, N. J., & Chabner, B. A. (1983) · New England Journal of Medicine · doi:10.1056/nejm198311033091805 · Cited by 786
Alitalo, K., Schwab, M., Lin, C. C., Varmus, H. E., & Bishop, J. M. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.6.1707 · Cited by 761
Transposition and amplification of oncogene-related sequences in human neuroblastomas
Kohl, N. E., Kanda, N., Schreck, R. R., Bruns, G., Latt, S. A., Gilbert, F., & Alt, F. W. (1983) · Cell · doi:10.1016/0092-8674(83)90169-1 · Cited by 731
GENETIC ANALYSIS OF THE MULTIDRUG TRANSPORTER
Gottesman, M. M., Hrycyna, C. A., Schoenlein, P. V., Germann, U. A., & Pastan, I. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.003135 · Cited by 478
Chromothripsis drives the evolution of gene amplification in cancer
Shoshani, O., Brunner, S. F., Yaeger, R., Ly, P., Nechemia-Arbely, Y., Kim, D. H., Fang, R., Castillon, G. A., Yu, M., Li, J. S. Z., et al. (2021) · Nature · doi:10.1038/s41586-020-03064-z · Cited by 469
Metadata
- Authors
- Kaufman, R. J., Brown, P. C., & Schimke, R. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1979-11
- Volume
- 76
- Issue
- 11
- Pages
- 5669-5673
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2042378550
- Cited by
- 376
- References
- 0
- FWCI
- 18.43
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. https://app.cochat.ai/papers/10.1073/pnas.76.11.5669
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- Kaufman, R. J., Brown, P. C., & Schimke, R. T. (1979). Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.76.11.5669
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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