DIETARY SELENIUM SUPPLEMENTATION PROLONGS SURVIVAL AND AMELIORATES THORACIC RADIATION‐INDUCED LUNG FIBROSIS IN MICE

Background Radiation induced pulmonary fibrosis is a devastating side effect of radiation therapy of intra‐thoracic malignancies; however there is currently no effective pharmacologic agent for its prevention. Since oxidative stress is implicated in the pathogenesis of lung fibrosis we hypothesized that augmenting the lung antioxidant defense by increasing dietary selenium intake prior to and following thoracic radiation in mice would ameliorate fibrosis. Selenium (Se) is a micronutrient, present in protective antioxidant selenoenzymes such as glutathione peroxidase (GPx). Methods We evaluated a 10‐fold supplemented Se diet (10X) as compared to a Se adequate (1X) and Se deficient (0X) diet (1.8 and 0.18 vs. 0.00 ppm Se, respectively) with respect to fibrosis and survival by 4 months post a single fraction 13.5 Gy thoracic X‐ray treatment (XRT). Mice (n=15 per group) were fed the respective diets at least 4 weeks prior to XRT to ensure augmented lung activity levels of GPx. Fibrosis was evaluated by lung hydroxyproline (OH‐Pro) and histology. Results OH‐Pro content of irradiated mouse lungs (μg/g lung) decreased significantly in the 10X‐Se group (89±2) and the 1X (113±4) as compared to the 0X (171±12). In addition, survival was significantly higher in the 10X irradiated group (80%) as compared to the 1X (66.7%) and the 0X (0%) group. Conclusion Selenium‐enriched diets may have a protective effect on the development of radiation fibrosis. Funded by: AICR and U. Penn Research Foundation (MCS)