Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications

Abstract

Purpose: Ionizing radiation (IR) is a ubiquitous environmental stressor with genotoxic and epigenotoxic capabilities. Terrestrial IR, predominantly a low-linear energy transfer (LET) radiation, is being widely utilized in medicine, as well as in multiple industrial applications. Additionally, an interest in understanding the effects of high-LET irradiation is emerging due to the potential of exposure during space missions and the growing utilization of high-LET radiation in medicine.

Conclusions: In this review, we summarize the current knowledge of the effects of IR on DNA methylation, a key epigenetic mechanism regulating the expression of genetic information. We discuss global, repetitive elements and gene-specific DNA methylation in light of exposure to high and low doses of high- or low-LET IR, fractionated IR exposure, and bystander effects. Finally, we describe the mechanisms of IR-induced alterations to DNA methylation and discuss ways in which that understanding can be applied clinically, including utilization of DNA methylation as a predictor of response to radiotherapy and in the manipulation of DNA methylation patterns for tumor radiosensitization.

Keywords:

• Epigenetics
• ionizing radiation
• DNA methylation
• radiotherapy
• space radiation
• transposable elements

Acknowledgements

The authors are thankful to Dr Janet Baulch for critical reading and to Christopher Fettes for editing this manuscript.

Disclosure statement

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

Additional information

Funding

Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number 1P20GM109005; NIH/UAMS Clinical and Translational Science Award UL1TR000039 and KL2TR000063, the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000, and the National Space Biomedical Research Institute through the National Aeronautics and Space Administration NCC 9-58, grant# RE03701.