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Taxol resistant mutants of Chinese hamster ovary cells: Genetic biochemical, and cross‐resistance studies

Taxol resistant mutants of Chinese hamster ovary cells: Genetic biochemical, and cross‐resistance... 10.1002/jcp.1041140122.abs The effects of the microtubule inhibitor taxol on the growth and viability of Chinese hamster ovary (CHO) cells have been examined. Stable mutants which are between seven to 11‐fold more resistant to taxol have been selected in a single step from ethyl methanesulfonate‐mutagenized CHO cells. The two taxol‐resistant mutants (TaxR‐1 and TaxR‐2) which have been studied in detail exhibit novel and strikingly different cross‐resistance/collateral sensitivity patterns to various microtubule inhibitors. For example, the TaxR‐1 mutant exhibits increased resistance to vinblastine, but in comparison to the parental cells, it shows enhanced sensitivity toward colchicine, colcemid, stegnacine, and griseofulvin. However, the sensitivity of this mutant toward other unrelated compounds, e.g., puromycin, daunomycin, etc., remained largely unaltered. The specific pattern of cross‐resistance/collateral‐sensitivity of this mutant toward various microtubule inhibitors suggests that the genetic lesion in this mutant may be affecting a microtubule‐related component. The TaxR‐2 mutant, in contrast, is highly resistant to various microtubule inhibitors including colchicine, colcemid, stegnacine, maytan‐sine, vinblastine, and podophyllotoxin. This mutant also exhibits greatly increased cross‐resistance to daunomycin, puromycin, ethidium bromide, and VM‐26 (compounds which do not inhibit microtubule assembly), and shows reduced cellular uptake of 3H‐daunomycin indicating that the genetic lesion in this mutant nonspecifically affects the membrane permeability of various drugs. The cell hybrids formed between TaxR‐1 (or TaxR‐2 mutant(s)) and a taxol‐sensitive cell line exhibit intermediate levels of resistance to the drug, indicating that the TaxR phenotypes of both these mutants behave codominantly under these conditions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

Taxol resistant mutants of Chinese hamster ovary cells: Genetic biochemical, and cross‐resistance studies

Journal of Cellular Physiology , Volume 114 (1) – Jan 1, 1983

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References (28)

Publisher
Wiley
Copyright
Copyright © 1983 Wiley‐Liss, Inc.
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/jcp.1041140122
pmid
6131076
Publisher site
See Article on Publisher Site

Abstract

10.1002/jcp.1041140122.abs The effects of the microtubule inhibitor taxol on the growth and viability of Chinese hamster ovary (CHO) cells have been examined. Stable mutants which are between seven to 11‐fold more resistant to taxol have been selected in a single step from ethyl methanesulfonate‐mutagenized CHO cells. The two taxol‐resistant mutants (TaxR‐1 and TaxR‐2) which have been studied in detail exhibit novel and strikingly different cross‐resistance/collateral sensitivity patterns to various microtubule inhibitors. For example, the TaxR‐1 mutant exhibits increased resistance to vinblastine, but in comparison to the parental cells, it shows enhanced sensitivity toward colchicine, colcemid, stegnacine, and griseofulvin. However, the sensitivity of this mutant toward other unrelated compounds, e.g., puromycin, daunomycin, etc., remained largely unaltered. The specific pattern of cross‐resistance/collateral‐sensitivity of this mutant toward various microtubule inhibitors suggests that the genetic lesion in this mutant may be affecting a microtubule‐related component. The TaxR‐2 mutant, in contrast, is highly resistant to various microtubule inhibitors including colchicine, colcemid, stegnacine, maytan‐sine, vinblastine, and podophyllotoxin. This mutant also exhibits greatly increased cross‐resistance to daunomycin, puromycin, ethidium bromide, and VM‐26 (compounds which do not inhibit microtubule assembly), and shows reduced cellular uptake of 3H‐daunomycin indicating that the genetic lesion in this mutant nonspecifically affects the membrane permeability of various drugs. The cell hybrids formed between TaxR‐1 (or TaxR‐2 mutant(s)) and a taxol‐sensitive cell line exhibit intermediate levels of resistance to the drug, indicating that the TaxR phenotypes of both these mutants behave codominantly under these conditions.

Journal

Journal of Cellular PhysiologyWiley

Published: Jan 1, 1983

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