Background The International Commission on Radiological Protection’s system of radiological protection (SRP) is mainly based on the linear no-threshold (LNT) hypothesis for radiation-induced cancer (radcancer). Objective To further demonstrate the invalidity of the LNT hypothesis for total-cancer absolute risk AR ( D ) as a function of the above natural background radiation absorbed dose D and provide a theoretical foundation for an improved SRP, based on a nonlinear threshold dose-response relationship for radcancer absolute risk AR r ( D ). Approach Use high signal-to-noise ratio (SNR) pituitary-tumor cancer-prevention data from a gamma-ray study with > 15000 mice and Bayesian-inference-related stochastic-threshold modeling to characterize the dose-response relationships for the total cancer prevention TP ( D ) probability, AR ( D ) (=1 – TP ( D )), and AR r ( D ). Results A non-monotonic relationship for TP ( D ) and a population-threshold ( D t )-multimodal relationship for AR r ( D ) were found, which represent dose-response shapes for these endpoints for all cancer types, for the dose range modeled. For D < D t only hormetic outcomes ( TP ( D ) > P 0 ) occur, where P 0 is the genomic-stress-adaptation (gensadaptation)-linked baseline cancer prevention probability. Conclusions AR r ( D ) is not an LNT or linear-quadratic or sigmoidal function of dose. Below D t , D can reduce the population exposome-histories (expohistories)-related baseline-cancer absolute risk AR 0 .
Objectives To investigate how graded early-life dietary restriction (DR) influences radiation-induced adaptive responses (AR), genotoxicity, lethality, and oxidative stress in a mouse model. Methods Female C57BL/6J mice were subjected to 25%, 50%, or 75% DR beginning immediately after weaning. Radiation adaptive responses were evaluated using a classical priming/challenge protocol. Survival after total-body irradiation, micronucleus formation, and reactive oxygen species (ROS) production in bone marrow cells were assessed. Results Mild DR (25%) preserved both survival and cytogenetic adaptive responses despite increased radiosensitivity. Moderate DR (50%) did not exhibit a detectable survival AR while preserving cytogenetic adaptation. Severe DR (75%) did not exhibit detectable survival or cytogenetic ARs and showed increased radiation-induced lethality and genotoxicity. Moderate DR also increased baseline and radiation-induced ROS levels. Conclusion Early-life nutritional status significantly modifies radiation responses in a severity- and endpoint-dependent manner in mice. These findings identify nutritional status as an important biological modifier of radiation response and suggest that developmental nutritional conditions may contribute to variability in radiation sensitivity. Further studies using clinically relevant models are needed to determine the translational implications of these findings.
Annual dose limits provide a practical basis for radiation protection, but a calendar year is not necessarily a biologically meaningful interval. Cellular repair, adaptive responses, and dose-rate effects may alter outcomes when the same total dose is delivered in different patterns. Conversely, rapid repair of measurable damage does not establish the absence of delayed effects or justify higher permissible doses. We propose research into temporally resolved exposure metrics that could complement cumulative dose accounting. Any regulatory change would require evidence linking exposure patterns to relevant health outcomes.
Objective To compare and validate dicentric chromosomes and centric rings (dic+r) dose-response calibration curves generated by manual (MS), semi-automated (SAS), and fully automated (FAS) scoring following 137 Cs γ-ray irradiation. Methods Peripheral blood samples from three healthy donors were irradiated with 137 Cs γ-rays (0–5.0 Gy). After lymphocyte culture, dic+r were scored using MS, SAS, and FAS. Linear-quadratic calibration curves were established using Biodose Tools and validated with blinded samples. Results All methods generated well-fitted linear-quadratic calibration curves ( R 2 > 0.99). Despite differences in fitted coefficients, comparable dose-response relationships were obtained. Validation using blinded samples demonstrated good agreement between estimated and delivered doses, with relative deviations below 20.0% for all methods. SAS showed high dose estimation accuracy, whereas FAS satisfied triage criteria above 1.0 Gy and substantially improved scoring throughput. Compared with MS, FAS and SAS increased throughput by approximately 22-fold and 6-fold, respectively. Conclusion SAS achieved dose estimation accuracy comparable to MS while substantially improving efficiency, whereas FAS enables rapid, high-throughput biodosimetry for radiation emergency triage, supporting a tiered strategy for large-scale radiation emergency response.
