Low-dose Ionizing Radiation Induces Oxidative Stress through Sirtuin 1-mediated Acetylation of Forkhead Box Protein O1 in the Human B-lymphoblastoid Cell Line IM-9.

With the increasing use of computed tomography, the biological effects of low-dose ionizing radiation (LDIR) have gained attention. However, its effects on B lymphocytes remain understudied. We investigated LDIR-induced oxidative stress in lymphocytes to establish a theoretical basis for clinical radiation safety. First, we demonstrated that LDIR induces a rapid oxidative response in the human B-lymphoblastoid cell line IM-9. Reactive oxygen species (ROS) levels increased at 0.25 h and decreased at 1 h after LDIR. In parallel, the number and intensity of γ-H2A.X and 53BP1 DNA damage foci significantly increased in the irradiated group. Transcriptome analysis identified Forkhead box protein O1 (FOXO1) as a key gene. Western blotting analysis showed that Sirtuin-1 (SIRT1) activity decreased at 0.25 h after irradiation, while the activity of FOXO1 and acetylated FOXO1 increased. Superoxide dismutase 2 (SOD2) activity decreased initially and then increased at 1 h. A co-immunoprecipitation (Co-IP) assay confirmed the interaction between FOXO1 and SIRT1, supporting their coordinated role in oxidative regulation. LDIR induced oxidative stress via the SIRT1/FOXO1 axis. These results demonstrate that early ROS accumulation suppresses SIRT1 activity, impedes FOXO1 deacetylation, and transiently reduces SOD2 activity, followed by a compensatory induction of SOD2 to restore redox balance.