Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

Abstract

Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI).

Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis; however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in messenger RNA (mRNA) levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesise that epigenetics may be the missing link in understanding the mechanism behind RIGI.

Keywords:

• ionising radiation
• genomic instability
• epigenetics
• DNA methylation
• chromatin remodelling
• MicroRNA

Acknowledgements

This work was supported by NASA grants NNJ06HD31G (WFM/JEB) and NNX07AT42G (JEB), and by Battelle Memorial Institute, Pacific Northwest Division, under Contract No. DE-AC05-76RL0 1830 with the U.S. Department of Energy (DOE), Office of Biological and Environmental Research (OBER) Low Dose Science Program. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.