Old Data—New Concepts: Integrating “Indirect Effects” Into Radiation Protection

Abstract Purpose: To address the following key question, what are the consequences of nontargeted and delayed effects for linear nonthreshold models of radiation risk? This paper considers low-dose “indirect” or nontargeted effects and how they might impact radiation protection, particularly at the level of the environment. Nontargeted effects refer to effects in cells, tissues, or organisms that were not targeted by irradiation and that did not receive direct energy deposition. They include genomic instability and lethal mutations in progeny of irradiated cells and bystander effects in neighboring cells, tissues, or organisms. Low-dose hypersensitivity and adaptive responses are sometimes included under the nontargeted effects umbrella, but these are not considered in this paper. Some concepts emerging in the nontargeted effects field that could be important include historic dose. This suggests that the initial exposure to radiation initiates the instability phenotype which is passed to progeny leading to a transgenerational radiation-response phenotype, which suggests that the system response rather than the individual response is critical in determining outcome. Conclusion: Nontargeted effects need to be considered, and modeling, experimental, and epidemiological approaches could all be used to determine the impact of nontargeted effects on the currently used linear nonthreshold model in radiation protection.