DNA damage at respiratory distress, but not acute time-points, correlates with tissue fibrosis following thoracic radiation exposure in mice

Purpose: Radiation exposure can result in DNA damage but whether the extent of DNA damage correlates with the radiation-induced tissue injury in the lung is not known. We aimed to determine whether numbers of gamma H2AX foci, representing histone H2AX phosphorylation a marker of DNA damage, measured within days of radiation exposure, correlated with known later lung injury responses in eight inbred mouse strains. Materials and methods: Mice received 18 Gy pulmonary irradiation and numbers of gamma H2AX positive nuclei in the lung were immunohistochemically determined. Results: Numbers of gamma H2AX foci, assessed up to seven days post irradiation did not correlate with pulmonary fibrosis. gamma H2AX counts from mice in respiratory distress, however, significantly correlated with fibrosis and lungs from mice treated with a fibrosis-reducing antagonist had fewer gamma H2AX foci. Conclusions: Acute response measures of pulmonary DNA damage did not predict for pathology, but levels of this marker in distressed mice were correlative of fibrosis.