Evolving paradigms for the biological response to low dose ionizing radiation; the role of epigenetics

Abstract

Purpose: In the late 1990s, it had become clear that the long-standing paradigm for the action of radiation on living cells and organisms did not have sufficient power to explain the observed effects of low dose ionizing radiation. The purpose of this commentary is to examine the experiments that lead up to the modification of the classic paradigm consequent on these observations, their historical precedents, and the development of our understanding of the role of epigenetics in low dose radiation effects.

Results and conclusions: We discuss how parallel advances in epigenetics from developmental biology and cancer studies, and the discovery of epigenetic modifications of chromatin, such as DNA methylation, impacted on the development of an epigenetic paradigm for low dose effects. We also assess the impact of technology development in supporting the paradigm shift. We then examine recent accumulated data on epigenetic modification in response to irradiation since that shift took place, and identify areas where bringing together data from developmental biology and cancer might answer some of the paradoxes and contradictions in this data. We predict that further paradigm shifts are imminent.

Keywords:

• Low dose radiation
• epigenetics
• DNA methylation
• non-targeted-effects

Acknowledgements

The authors are grateful to Profs. Carmel Mothersill and Jonathan Bard for comments and critical reading of the manuscript. In addition, our understanding of the development of these ideas has benefited greatly from discussions over the years with Profs John Hopewell, Colin Seymour, Christian Streffer, Keith Baverstock, and Bill Morgan.

Disclosure statement

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

Notes on contributors

Paul N. Schofield is the University Reader in Biomedical Informatics at the University of Cambridge. His research focus is on experimental and informatic approaches to understanding human disease using model organisms. He has a long-standing interest in mammalian epigenetics and the biological effects of low dose ionising radiation.

Monika Kondratowicz is a post-graduate medical student at the University of Cambridge.