Abstract

The present system of radiation protection assumes that exposure at low doses and/or low dose-rates leads to health risks linearly related to the dose. They are evaluated by a combination of epidemiological data and radiobiological models. The latter imply that radiation induces deleterious effects via genetic mutation caused by DNA damage with a linear dose-dependence. This picture is challenged by the observation of radiation-induced epigenetic effects (changes in gene expression without altering the DNA sequence) and of non-linear responses, such as non-targeted and adaptive responses, that in turn can be controlled by gene expression networks. Here, we review important aspects of the biological response to ionizing radiation in which epigenetic mechanisms are, or could be, involved, focusing on the possible implications to the low dose issue in radiation protection. We examine in particular radiation-induced cancer, non-cancer diseases and transgenerational (hereditary) effects. We conclude that more realistic models of radiation-induced cancer should include epigenetic contribution, particularly in the initiation and progression phases, while the impact on hereditary risk evaluation is expected to be low. Epigenetic effects are also relevant in the dispute about possible “beneficial” effects at low dose and/or low dose-rate exposures, including those given by the natural background radiation.

Highlights

  • There is increasing interest in assessing the robustness of the present system of radiation protection at low doses and/or low dose-rates, typical of those exposures encountered in the workplace, in the environment and in diagnostic medicine

  • Some important general notions are currently used by international bodies, such as the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and the International Commission on Radiological Protection (ICRP), to extrapolate to low doses and low dose rates the health risk derived from epidemiological data at higher acute doses

  • A recent review pointed to the radiation-induced oxidative stress as the source of various processes connected to adaptive response (AR) [170], which is consistent with the occurrence of epigenetic mechanisms

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Summary

Introduction

There is increasing interest in assessing the robustness of the present system of radiation protection at low doses and/or low dose-rates, typical of those exposures encountered in the workplace, in the environment and in diagnostic medicine ( irradiation of normal tissues in radiotherapy may fall in this type of exposure). Some important general notions are currently used by international bodies, such as the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and the International Commission on Radiological Protection (ICRP), to extrapolate to low doses and low dose rates the health risk derived from epidemiological data at higher acute doses. These notions are essentially the harmful mutagenic potential of ionizing radiation and its linear dose-dependence at low levels of exposure [1,2]. The present review encompasses many important aspects of the biological response to ionizing radiation in which epigenetic mechanisms are shown to be, or could likely be, involved with a focus on the possible implications in health risk assessment at low doses, a key issue in radiation protection

The Current Paradigm of Radiation Biology
Challenges to the Current Paradigm
The Main Epigenetic Modifications
Radiation-Induced Changes in DNA Methylation
Radiation-Induced Histone Modifications
Radiation-Induced Modulation of Non-Coding RNA Expression
Radiation Quality May Affect Epigenetic Changes
Basic Mechanisms of Radiation-Induced Epigenetic Changes
Epigenetic Changes Have a Role in Radiation-Induced NTE and AR
Radiation-Induced Cancer
Transgenerational Effects
Non Cancer Effects
Possible Epigenetic Role in Radiation-Induced Cognitive Effects
Possible Epigenetic Role in Radiation-Induced Cardiovascular Effects
Possible Epigenetic Role in Radiation-Induced Cataract
Epigenetics Is Needed in Radiobiology Paradigms
Implications in Radiation-Induced Hereditary Effects
Implications in Radiation-Induced Non-Cancer Effects
Findings
Low-Level Exposures
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