CaltechAUTHORS
  A Caltech Library Service

Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells

Roninson, Igor B. and Abelson, Herbert T. and Housman, David E. and Howell, Neil and Varshavsky, Alexander (1984) Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature, 309 (5969). pp. 626-628. ISSN 0028-0836. doi:10.1038/309626a0. https://resolver.caltech.edu/CaltechAUTHORS:20210119-114432302

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20210119-114432302

Abstract

Mammalian cells selected for resistance to certain cytotoxic drugs frequently develop cross-resistance to a broad spectrum of other drugs unrelated in structure to the original selective agent. This phenomenon constitutes a major problem in cancer chemotherapy. Multi-drug resistance arises from decreased intracellular drug accumulation, apparently due to an alteration of the plasma membrane. The observation of double minute chromosomes or homogeneously staining regions in some of the multi-drug-resistant cell lines suggests that gene amplification underlies this phenomenon. We have used the technique of DNA renaturation in agarose gels to detect, compare and clone amplified DNA sequences in Adriamycin- and colchicine-resistant sublines of Chinese hamster cells. We show that both Adriamycin- and colchicine-resistant cells contain amplified DNA fragments, some of which are amplified in both of these independently derived cell lines. Furthermore, loss of the multi-drug resistance phenotype on growth in the absence of drugs correlates with the loss of amplified DNA. These results strongly suggest that the DNA sequences which are amplified in common in multi-drug-resistant cell lines include the gene(s) responsible for a common mechanism of multi-drug resistance in these cells. We have cloned one of the commonly amplified DNA fragments and show that the degree of amplification of this fragment in the cells correlates with the degree of their drug resistance.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/309626a0DOIArticle
https://rdcu.be/cdRikPublisherFree ReadCube access
ORCID:
AuthorORCID
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1984 Nature Publishing Group. Received 23 January: accepted 2 April 1984. We thank Carolyn Gorka for technical assistance and Cathy Thurmond for typing the manuscript. This work was supported by NIH grants CA33297 (A.V.), CA18662 (H.T.A.), CA17575 (D.E.H.) and CA28608 (N.H.). I.B.R. is the recipient of a postdoctoral fellowship from the American Cancer Society.
Funders:
Funding AgencyGrant Number
NIHCA33297
NIHCA18662
NIHCA17575
NIHCA28608
American Cancer SocietyUNSPECIFIED
Issue or Number:5969
DOI:10.1038/309626a0
Record Number:CaltechAUTHORS:20210119-114432302
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210119-114432302
Official Citation:Roninson, I., Abelson, H., Housman, D. et al. Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature 309, 626–628 (1984). https://doi.org/10.1038/309626a0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107537
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:19 Jan 2021 20:25
Last Modified:16 Nov 2021 19:04

Repository Staff Only: item control page