Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors
- 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), Vol. 49; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
Similar Records
Induction of DNA double-strand breaks by restriction enzymes in X-ray-sensitive mutant Chinese hamster ovary cells measured by pulsed-field gel electrophoresis
Chromosomal damage observed in first postirradiation metaphases of repair-proficient and -deficient cell lines
Related Subjects
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