Dotting the eyes: mouse strain dependency of the lens epithelium to low dose radiation-induced DNA damage

Stephen Barnard*, Jayne Moquet, S. Lloyd, Michele Ellender, Elizabeth Ainsbury, R. A. Quinlan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Purpose: Epidemiological evidence regarding the radiosensitivity of the lens of the eye and radiation cataract development has led to changes in the EU Basic Safety Standards for protection of the lens against ionizing radiation. However, mechanistic details of lens radiation response pathways and their significance for cataractogenesis remain unclear. Radiation-induced DNA damage and the potential impairment of repair pathways within the lens epithelium, a cell monolayer that covers the anterior hemisphere of the lens, are likely to be involved. Materials and Methods: In this work, the lens epithelium has been analyzed for its DNA double-strand break (DSB) repair response to ionizing radiation. The responses of epithelial cells located at the anterior pole (central region) have been compared to at the very periphery of the monolayer (germinative and transitional zones). Described here are the different responses in the two regions and across four strains (C57BL/6, 129S2, BALB/c and CBA/Ca) over a low dose (0–25 mGy) in-vivo whole body X-irradiation range up to 24 hours post exposure. Results: DNA damage and repair as visualized through 53BP1 staining was present across the lens epithelium, although repair kinetics appeared non-uniform. Epithelial cells in the central region have significantly more 53BP1 foci. The sensitivities of different mouse strains have also been compared. Conclusions: 129S2 and BALB/c showed higher levels of DNA damage, with BALB/c showing significantly less inter-individual variability and appearing to be a more robust model for future DNA damage and repair studies. As a result of this study, BALB/c was identified as a suitable radiosensitive lens strain to detect and quantify early low dose ionizing radiation DNA damage effects in the mouse eye lens specifically, as an indicator of cataract formation.

Original languageEnglish
Pages (from-to)1116-1124
Number of pages9
JournalInternational Journal of Radiation Biology
Volume94
Issue number12
DOIs
Publication statusPublished - 2 Dec 2018

Bibliographical note

Funding Information:
The authors would like to thank Kevin Whitehill and Christopher Ottaway of PHE for technical support and advice.

Publisher Copyright:
© 2018, Copyright © 2018 Taylor & Francis Group LLC.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • DNA damage
  • cataracts
  • eye
  • low dose effects
  • radiation protection

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