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

Journal Article · Fri Dec 15 04:00:00 EST 1989 · Cancer Research; (USA)

OSTI ID:5032040

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

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

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.

• OSTI ID: 5032040
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 49; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

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