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...