Biochemical and cytogenetical characterization of Chinese hamster ovary X-ray-sensitive mutant cells xrs 5 and xrs 6 VI. The correlation between UV-induced DNA lesions and chromosomal aberrations, and their modulations with inhibitors of DNA repair synthesis
| Autor: | G.P. van der Schans, Firouz Darroudi, Adayapalam T. Natarajan |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
DNA Replication
DNA Repair Ultraviolet Rays DNA damage DNA repair Mutant DNA Single-Stranded Biology Toxicology medicine.disease_cause Radiation Tolerance Cell Line chemistry.chemical_compound Cricetulus Cricetinae Genetics medicine Animals Hydroxyurea Molecular Biology Chromosome Aberrations Mutation X-Rays Chinese hamster ovary cell Cytarabine DNA replication DNA Molecular biology chemistry Cell culture DNA Damage |
| Zdroj: | Mutation Research/DNA Repair. 235:129-135 |
| ISSN: | 0921-8777 |
| DOI: | 10.1016/0921-8777(90)90066-e |
| Popis: | The role of UV-induced DNA lesions and their repair in the formation of chromosomal aberrations in the xrs mutant cell lines xrs 5 and xrs 6 and their wild-type counterpart, CHO-K1 cells, were studied. The extent of induction of DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) due to UV irradiation in the presence or absence of 1-beta-D-arabinofuranosylcytosine (ara-C) and hydroxyurea (HU) was determined using the alkaline and neutral elution methods. Results of these experiments were compared with the frequencies of induced chromosomal aberrations in UV-irradiated G1 cells treated under similar conditions. Xrs 6 cells showed a defect in their ability to perform the incision step of nucleotide repair after UV irradiation. Accumulation of breaks 2 h after UV irradiation in xrs 6 cells in the presence of HU and ara-C remained at the level of incision breaks estimated after 20 min, which was about 35% of that found in wild-type CHO-K1 cells. In UV-irradiated CHO-K1 and xrs 5 cells, more incision breaks were present after 2 h compared with 20 min post-treatment with ara-C, a further increase was evident when HU was added to the combined treatment. The level of incision breaks induced under these conditions in xrs 5 was about 80% of that observed in CHO-K1 cells. UV irradiation itself did not induce any detectable DNA strand breaks. Accumulation of SSBs in UV-irradiated cells post-treated with ara-C and HU coincides with the increase in the frequency of chromosomal aberrations. These data suggest that accumulated SSBs when converted to DSBs in G1 give rise to chromosome-type aberrations, whereas strand breaks persisting until S-phase result in chromatid-type aberrations. Xrs 6 appeared to be the first ionizing-radiation-sensitive mutant with a partial defect in the incision step of DNA repair of UV-induced damage. |
| Databáze: | OpenAIRE |
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