title: DNA damage at respiratory distress, but not acute time-points, correlates with tissue fibrosis following thoracic radiation exposure in mice.
abstract: OBJECTIVE
  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 γH2AX 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.
  
  
  METHODS
  Mice received 18 Gy pulmonary irradiation and numbers of γH2AX positive nuclei in the lung were immunohistochemically determined.
  
  
  RESULTS
  Numbers of γH2AX foci, assessed up to seven days post irradiation did not correlate with pulmonary fibrosis. γH2AX counts from mice in respiratory distress, however, significantly correlated with fibrosis and lungs from mice treated with a fibrosis-reducing antagonist had fewer γH2AX 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.
authors.affiliation: Department of Human Genetics, McGill University , Montreal, QC , Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.forename: Christina K
authors.initials: CK
authors.lastname: Haston
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000528:radiation effects; D004249:DNA Damage; D006657:Histones / Q000032:analysis; D008168:Lung / Q000528:radiation effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011658:Pulmonary Fibrosis / Q000209:etiology*; D013045:Species Specificity; D013909:Thorax / Q000528:radiation effects
chemical_list: C468783:H2AX protein, human; D006657:Histones
keywords: Inbred mouse strains; double-strand breaks; fibrosis; thoracic irradiation