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Bystander effects in radiation-induced genomic instability.
William F Morgan1, Andreas Hartmann, Charles L Limoli
1Radiation Oncology Research Laboratory, Department of Radiation Oncology and Program in Oncology, University of Maryland at Baltimore, BRB 6-011, 655 W. Baltimore Street, Baltimore, MD 21201-1559, USA. wfmorgan@som.umaryland.edu
Mutation Research
|July 11, 2002
Summary
X-ray exposure causes chromosomal instability in hybrid cells. This instability arises from increased recombination at telomere-like sequences, not DNA breaks, potentially driven by reactive oxygen species.
Area of Science:
- Genetics
- Cell Biology
- Radiation Biology
Background:
- X-ray exposure can induce chromosomal instability in surviving cells.
- This instability involves dynamic cytogenetic rearrangements of human chromosomes in hybrid cells.
- The underlying mechanisms for persistent genomic instability require further investigation.
Purpose of the Study:
- To investigate elevated endogenous DNA breaks in chromosomally unstable clones.
- To determine if recombinational events involving interstitial telomere repeat-like sequences contribute to instability.
- To elucidate the mechanisms perpetuating radiation-induced genomic instability.
Main Methods:
- Comet assay to measure endogenous DNA breaks.
- Two-color fluorescence in situ hybridization (FISH) to detect recombination events.
- Analysis of chromosomal rearrangements in radiation-induced unstable clones.
Main Results:
- No significant difference in comet tail measurements between irradiated and non-irradiated unstable clones.
- Nine out of eleven unstable clones showed significantly higher than expected involvement of interstitial telomere repeat-like sequences at recombination junctions.
- Recombination events involving interstitial telomere repeat-like sequences were elevated in unstable clones.
Conclusions:
- Elevated endogenous DNA breaks do not account for the observed chromosomal instability.
- Recombinational events involving interstitial telomere repeat-like sequences are a key feature of instability.
- Epigenetic or bystander effects, potentially involving reactive oxygen species and a chronic pro-oxidant environment, likely perpetuate genomic instability across generations.