Inducible Nitric Oxide Synthase and Nitrotyrosine in Mice with Radiation-induced Lung Damage

The purpose of this study was to determine if radiation-induced lung damage is associated with induction of nitric oxide synthase (NOS) II and nitrotyrosine in an irradiated lung mouse model. The thorax of BALBc mice were exposed to 14 Gy radiation (experimental) or no radiation (control) and killed after at 1, 3, 6, 12, and 24 hours; 3, 15, and 30 days; and 3 and 6 months after treatment. Lung sections were processed for immunohistochemistry using NOS II and nitrotyrosine polyclonal antisera and in situ hybridization using 35S labeled probes for mouse NOS II. Quantitative analysis of experimental and control sections showed significant induction of NOS II and nitrotyrosine in alveolar macrophages from 6 hours to 30 days postirradiation, which was diminished by 3 months. The airway and alveolar epithelium and vascular endothelium showed strong NOS II expression at 15 to 30 days postirradiation. Nitrotyrosine immunostaining was also strongly evident in the alveolar epithelium and vascular endothelium during this period. There was little or no NOS II or nitrotyrosine in the sham control lungs throughout the study. These findings demonstrate increased formation of both NO and nitrotyrosine after radiation treatment and suggest a role for these molecules in the pathogenesis of radiation-induced lung damage.