Prenatal low-dose cesium-137 exposure combined with a lipid-enriched diet promotes late-onset hepatic tumorigenesis in male mouse offspring

Abstract Intrauterine life represents a sensitive period during which low‑dose radiation may shape long‑term health outcomes; however, its impact, particularly when combined with lifelong metabolic stressors such as a high‑fat diet (HFD) remains unclear. This study investigated whether prenatal exposure to low‑dose cesium‑137 influences hepatic outcomes in offspring. Pregnant C57BL/6J mice received cesium‑137 in drinking water throughout gestation (total dose: 100 mGy). After weaning, offspring were fed either a standard diet (SD) or HFD. Body and liver weights, plasma biochemistry, and tissue analyses were performed at 10 weeks and 15 months of age. Prenatal low‑dose irradiation (LDI) did not show major effects in offspring subjected to SD; however, it exacerbates HFD-induced adverse effects. A sex‑ and age‑dependent interaction with HFD emerged: At 15 months of age, irradiated males subjected to HFD showed a 2.8-fold increase in hepatic tumor incidence, accompanied by a significant elevation of ALT and AST levels, pronounced dyslipidemia (cholesterol and triglycerides), and a 2.5-fold upregulation of Myc proto-oncogene. These findings may represent the first evidence that intrauterine LDI increases susceptibility to HFD‑induced hepatic tumorigenesis in males, suggesting that LDI may cause a potential developmental disruption that creates a latent vulnerability manifesting later in life.