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

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.

Keywords:

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

Acknowledgements

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

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

S. G. R. Barnard

S. G. R. Barnard, BSc, is a radiation protection scientist at Public Health England and a PhD candidate with Durham University, UK.

J. Moquet

J. Moquet, PhD, is a principal radiation protection scientist at Public Health England.

S. Lloyd

S. Lloyd, MSc, is visiting masters student at Public Health England and masters candidate at Birmingham University, UK.

M. Ellender

M. Ellender, PhD, is a principal radiation protection scientist at Public Health England.

E. A. Ainsbury

E. A. Ainsbury, PhD, a group leader of the cytogenetics and biomarkers research goup at Public Health England.

R. A. Quinlan

R. A. Quinlan, PhD, as a professor in the department of biosciences at Durham University, UK.