Impact of Low-Dose X-Ray Radiation Exposure on Lung Cancer Progression

Low-dose ionizing radiation is known to alter the biological properties of tumor cells. Although clinical computed tomography delivers low-dose radiation, the long-term radiobiological impacts of repeated low-dose X-ray exposure on the malignant progression of lung adenocarcinoma remain poorly defined and require further preclinical clarification. In this preclinical study, we established long-term passaged A549 lung adenocarcinoma cell models subjected to single and fractionated low-dose X-ray irradiation. In vitro functional phenotypes and molecular alterations were further evaluated using murine subcutaneous xenograft and tail vein pulmonary colonization models to assess tumor growth and lung colonization capacity. Long-term low-dose irradiation significantly promoted lung cancer cell proliferation and migration in vitro and enhanced tumor growth and pulmonary colonization in mice. The results for cells cultured in vitro showed that low-dose radiation induced persistent DNA damage responses, modulated p53 expression, and upregulated the expression of epithelial-mesenchymal transition (EMT)- and glycolysis-related proteins, thereby remodeling the aggressive malignant phenotype of lung adenocarcinoma cells. Prolonged low-dose X-ray exposure drives progressive malignant phenotypic remodeling in A549 cells. Our work provides experimental radiobiological evidence of radiation-promoted tumor progression. Importantly, these preclinical findings are restricted to cell culture and animal models and cannot be directly extrapolated to clinical situations.