Bystander effects in radiation-induced genomic instability.
Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.
Morgan
William F
WF
Radiation 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
Hartmann
Andreas
A
Limoli
Charles L
CL
Nagar
Shruti
S
Ponnaiya
Brian
B
D000818:Animals; D024201:Bystander Effect / Q000235:genetics / Q000528:radiation effects*; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects*; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence
D004247:DNA