Gene amplification-associated cytogenetic aberrations and protein changes in vincristine-resistant chinese hamster, mouse, and human cells Journal Article
| Authors: | Meyers, M. B.; Spengler, B. A.; Chang, T. D.; Melera, P. W.; Biedler, J. L. |
| Article Title: | Gene amplification-associated cytogenetic aberrations and protein changes in vincristine-resistant chinese hamster, mouse, and human cells |
| Abstract: | We carried out cytogenetic studies of four Chinese hamster, mouse, and human cell lines selected for high levels of resistance (500- to 4,000-fold) to vincristine (VCR) by a multistep selection procedure. All cells examined contained gene amplification-associated metaphase chromosome abnormalities, either homogeneously staining regions (HSRs), abnormally banding regions (ABRs), or double-minute chromosomes (DMs); control actinomycin D- and daunorubicin-resistant hamster lines did not exhibit this type of chromosomal abnormality. VCR-resistant Chinese hamster sublines exhibited both increased synthesis of the protein V19 (Mr 19,000; pl = 5.7) and increased concentrations of V19 polysomal mRNA. When VCR-resistant cells were grown in drug-free medium, level of resistance, synthesis of V19, and amount of V19 mRNA declined in parallel with mean length of the HSR or mean number of DMs per cell. Cross-resistance studies indicate that VCR-resistant cells have increased resistance both to antimitotic agents and to a wide variety of agents unrelated to VCR in chemical structure and/or mechanism of action. Our studies of tubulin synthesis in Chinese hamster cells indicate no overproduction of tubulin or presence of a mutant tubulin species. Comparison with antifolate-resistant Chinese hamster cells known to contain amplified dihydrofolate reductase genes localized to HSRs or ABRs strongly suggests that the HSRs, ABRs, or DMs of the Vinca alkaloid-resistant sublines likewise represent cytological manifestations of specifically amplified genes, possibly encoding V19, involved in development of resistance to VCR. © 1985, Rockefeller University Press., All rights reserved. |
| Keywords: | human cell; nonhuman; animals; mice; cell cycle; heredity; gene amplification; cell line; protein; vincristine; in vitro study; drug resistance; chromosome aberration; cell culture; chromosome aberrations; molecular weight; normal human; female genital system; cricetinae; cricetulus; cricetulus griseus; chemical mutagenesis; humans; human; priority journal; isoelectric point; vinca |
| Journal Title: | Journal of Cell Biology |
| Volume: | 100 |
| Issue: | 2 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1985-02-01 |
| Start Page: | 588 |
| End Page: | 597 |
| Language: | English |
| DOI: | 10.1083/jcb.100.2.588 |
| PUBMED: | 3968181 |
| PROVIDER: | scopus |
| PMCID: | PMC2113449 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
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