Abstract
Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation (e.g. energy depositions and ionizations in the nucleus) and undamaged “bystander” cells, sometimes over long distances. Their consequences, called non-targeted effects (NTE), can substantially contribute to radiation-induced damage (e.g. cell death, genomic instability, carcinogenesis), particularly at low doses/dose rates (e.g. space exploration, some occupational and accidental exposures). In addition to controlled laboratory experiments, analysis of observational data on wild animal and plant populations from areas contaminated by radionuclides can enhance our understanding of radiation responses because such data span wide ranges of dose rates applied over many generations. Here we used a mechanistically-motivated mathematical model of TE and NTE to analyze published embryonic mortality data for plants (Arabidopsis thaliana) and rodents (Clethrionomys glareolus) from the Chernobyl nuclear power plant accident region. Although these species differed strongly in intrinsic radiosensitivities and post-accident radiation exposure magnitudes, model-based analysis suggested that NTE rather than TE dominated the responses of both organisms to protracted low-dose-rate irradiation. TE were predicted to become dominant only above the highest dose rates in the data. These results support the concept of NTE involvement in radiation-induced health risks from chronic radiation exposures.
Highlights
Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation and undamaged “bystander” cells, sometimes over long distances
The signaling pathways involved in non-targeted effects (NTE) are complex and incompletely understood, their consequences can be quantitatively modeled by using the following set of assumptions: (1) irradiated cells “activate” other cells in an “on–off ” manner by NTE signals, causing them to enter into a prolonged stressed state, which can be transmitted across generations. (2) “Activated” cells accumulate damage at an elevated rate
Predicted radiation responses for various exposure scenarios with constant or exponentially decreasing dose rates, based on best fits of the model to each data set, are shown in Figs. 3 and 4 for plants and Figs. 5 and 6 for rodents. These results suggest that NTE rather than TE dominated the responses of both organisms to protracted low-dose-rate irradiation (Figs. 3, 5)
Summary
Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation (e.g. energy depositions and ionizations in the nucleus) and undamaged “bystander” cells, sometimes over long distances Their consequences, called non-targeted effects (NTE), can substantially contribute to radiation-induced damage (e.g. cell death, genomic instability, carcinogenesis), at low doses/dose rates (e.g. space exploration, some occupational and accidental exposures). Difficult to repair complex DNA lesions, such as clusters of DNA double strand breaks in close proximity to one another, potentially with accompanying single strand breaks and base damage, represent an important type of radiation damage which can induce persistent NTE signal release and other adverse o utcomes[25,26,27,28,29,30] Sometimes they are protective against ionizing radiation exposure (e.g. adaptive responses, terminal cell differentiation), but in other cases “overreactive” and persistent stress responses cause harmful outcomes (e.g. genomic instability, chronic inflammation)
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