Effects of Fractionated Low Dose Ionizing Radiation on Cellular Senescence in Mouse Lung Tissue

Fractionated low dose ionizing radiation (LDIR) can induce various biological effects, which are key potential triggers for the development of radiation-induced lung injury (RILI). This study aims to investigate the effects of fractionated LDIR on early-stage cellular senescence, as well as on the levels of oxidation-antioxidation and DNA damage repair, in mouse lung tissue. C57BL/6J mice were exposed to fractionated LDIR, and subsequent assays were performed to evaluate the biological effects. Compared with the control group, mice in all dose groups showed the following changes: varying degrees of pathological alterations in lung tissue; elevated SA-β-Gal activity and upregulated expression of senescence-related genes in lung tissue; increased serum levels of urea, blood glucose (BG), and triglycerides (TG), along with reduced high-density lipoprotein cholesterol (HDL-C) levels; increased levels of oxidative damage markers in lung tissue, accompanied by elevated total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity, but decreased reduced glutathione (GSH) levels; upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genes; and increased DNA damage markers in lung tissue, as well as elevated mRNA and protein levels of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). The oxidative damage and DNA damage potentially induced by fractionated LDIR exceeded the compensatory capacity of the repair systems, probably leading to a dual dynamic imbalance in both oxidation-antioxidation and DNA damage repair. These may contribute to the progression of cellular senescence in lung tissue and the initiation of early-stage RILI.