Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors

Jeggo, P A; Caldecott, K; Pidsley, S; Banks, G R

Title: Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors

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Abstract

xrs-1 is an ionizing radiation sensitive Chinese hamster ovary (CHO) strain and has a defect in double strand break rejoining. It is also highly sensitive to topoisomerase II inhibiting anticancer drugs. Sensitivity is specific for those drugs that inhibit the breakage/reunion mechanism of topoisomerase II. xrs-1 and its parent strain CHO-K1 have equal levels of topoisomerase II activity, assayed by their ability to unknot complex knotted P4 head DNA. Drug stimulated protein-DNA complex formation was similar in xrs-1 and CHO-K1, showing that they accrued equal levels of drug induced lesions. Thus sensitivity most likely results from subsequent differences in the processing of these lesions rather than the rate of formation. Drug sensitivity is directly related to the xrs phenotype since drug and gamma-ray resistance are coordinately reactivated by azacytidine treatment. All six members of the xrs complementation group are hypersensitive to etoposide. Sensitivity is not a feature common to all X-ray sensitive mutants but is shown by another complementation group, which also has a defect in double strand break rejoining. These results thus demonstrate a correlation between an inability to rejoin double strand breaks and sensitivity to topoisomerase II targeting antitumor drugs.

Authors:

Jeggo, P A; Caldecott, K; Pidsley, S; Banks, G R ^[1]

National Institute for Medical Research, Ridgeway, Mill Hill, London (England)

Publication Date:: Fri Dec 15 00:00:00 EST 1989

OSTI Identifier:: 5032040

Resource Type:: Journal Article

Journal Name:: Cancer Research; (USA)

Additional Journal Information:: Journal Volume: 49; Journal ID: ISSN 0008-5472

Country of Publication:: United States

Language:: English

Subject:: 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; CHO CELLS; DNA REPAIR; GENE MUTATIONS; RADIOINDUCTION; ANTINEOPLASTIC DRUGS; DNA; ELECTROPHORESIS; ENZYME INHIBITORS; GAMMA RADIATION; HAMSTERS; ISOMERASES; PHENOTYPE; RADIOSENSITIVITY; STRAND BREAKS; ANIMAL CELLS; ANIMALS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; DRUGS; ELECTROMAGNETIC RADIATION; ENZYMES; IONIZING RADIATIONS; MAMMALS; MUTATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; RADIATIONS; RECOVERY; REPAIR; RODENTS; VERTEBRATES; 560120* - Radiation Effects on Biochemicals, Cells, & Tissue Culture

Citation Formats


                    Jeggo, P A, Caldecott, K, Pidsley, S, and Banks, G R. Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors.  United States: N. p., 1989. 
        Web.

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                    Jeggo, P A, Caldecott, K, Pidsley, S, & Banks, G R. Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors.  United States.

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                    Jeggo, P A, Caldecott, K, Pidsley, S, and Banks, G R. 1989.  
        "Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors".  United States.

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@article{osti_5032040,

  title        = {Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors},

  author       = {Jeggo, P A and Caldecott, K and Pidsley, S and Banks, G R},

  abstractNote = {xrs-1 is an ionizing radiation sensitive Chinese hamster ovary (CHO) strain and has a defect in double strand break rejoining. It is also highly sensitive to topoisomerase II inhibiting anticancer drugs. Sensitivity is specific for those drugs that inhibit the breakage/reunion mechanism of topoisomerase II. xrs-1 and its parent strain CHO-K1 have equal levels of topoisomerase II activity, assayed by their ability to unknot complex knotted P4 head DNA. Drug stimulated protein-DNA complex formation was similar in xrs-1 and CHO-K1, showing that they accrued equal levels of drug induced lesions. Thus sensitivity most likely results from subsequent differences in the processing of these lesions rather than the rate of formation. Drug sensitivity is directly related to the xrs phenotype since drug and gamma-ray resistance are coordinately reactivated by azacytidine treatment. All six members of the xrs complementation group are hypersensitive to etoposide. Sensitivity is not a feature common to all X-ray sensitive mutants but is shown by another complementation group, which also has a defect in double strand break rejoining. These results thus demonstrate a correlation between an inability to rejoin double strand breaks and sensitivity to topoisomerase II targeting antitumor drugs.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/5032040},
  journal      = {Cancer Research; (USA)},

  issn         = {0008-5472},

  number       = ,

  volume       = 49,

  place        = {United States},

  year         = {Fri Dec 15 00:00:00 EST 1989},

  month        = {Fri Dec 15 00:00:00 EST 1989}

}

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