Supplementary file 1_Dasatinib and quercetin mitigate radiation-induced lung injury by eliminating senescent cells in a rat model.pdf

BackgroundRadiation-induced lung injury (RILI) is a major dose-limiting toxicity in thoracic radiotherapy, and accumulating evidence implicates radiation-induced cellular senescence in its pathogenesis. This study aimed to investigate whether combination therapy with dasatinib and quercetin (DQ) could mitigate RILI by reducing senescent cell burden.
MethodsA rat model of RILI was established using a single 30 Gy irradiation to the right lung. Pulmonary pathological changes, fibrosis, DNA damage, and cellular senescence were assessed by histology, immunofluorescence, senescence-associated β-galactosidase staining, Western blotting and immunohistochemistry. Transcriptomic profiling was performed to explore the underlying molecular mechanisms.
ResultsCompared with irradiation alone, DQ treatment significantly alleviated radiation-induced inflammatory cell infiltration and collagen deposition, reduced γH2AX levels, decreased senescence-associated markers p53, p21, and p16, and suppressed multiple senescence-associated secretory phenotype (SASP) factors. Transcriptomic analysis indicated that DQ-mediated effects were closely associated with activation of apoptotic pathways and modulation of p53, MAPK, PI3K-Akt and mitophagy signaling cascades.
ConclusionDQ attenuated RILI in rats, with effects consistent with the reduced radiation-induced senescent cells and suppression of senescence-associated inflammatory responses.