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

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.