DNA damage and genomic instability
- Univ. of California, San Francisco, CA (United States)
To investigate the role of DNA strand breakage as the molecular lesion responsible for initiating genomic instability, five different strand breaking agents; bleomycin, neocarzinostatin, hydrogen peroxide, restriction endonucleases and ionizing radiation were examined for their capacity to induce delayed chromosomal instability. These studies were carried out in GM10115 human-hamster hybrid cells which contain one copy of human chromosome 4 in a background of 20-24 hamster chromosomes. Chromosomal instability was investigated using fluorescence in situ hybridization to visualize chromosomal rearrangements involving human chromosome 4. Rearrangements are detected multiple generations post-treatment, in clonal populations derived from single progenitor cells surviving treatment to the specified DNA damaging agents. Analysis of over 250 individual clones representing over 50,000 metaphases clearly demonstrate that when compared at comparable levels of cell kill, ionizing radiation, bleomycin and neocarzinostatin are equally effective at eliciting delayed genomic instability. In contrast, the analysis of nearly 300 clones and 60,000 metaphases, involving treatment with four different restriction endonucleases and/or hydrogen peroxide did not show any manifestation of chromosomal instability. These data will be discussed in terms of treatment/DNA interactions.
- Research Organization:
- OAK (Oakland Operations Office, Oakland, CA)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC03-76SF01012
- OSTI ID:
- 530847
- Report Number(s):
- CONF-9704100--
- Journal Information:
- Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.28 Vol. 29; ISSN 0893-6692; ISSN EMMUEG
- Country of Publication:
- United States
- Language:
- English
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