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

Abstract

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 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.

Materials and 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.

Keywords::

• Inbred mouse strains
• double-strand breaks
• thoracic irradiation
• fibrosis

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This research was funded by a grant from the Canadian Institutes of Health Research (to CKH).