When the Body Is Unprepared: Dietary Restriction Alters Radiation-Induced Adaptive Response, Genotoxicity and Lethality in Mice

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.