Nonlinear ionizing radiation-induced changes in eye lens cell proliferation, cyclin D1 expression and lens shape

Ewa Markiewicz, Stephen Barnard, Jacqueline Haines, Margaret Coster, Orry Van Geel, Weiju Wu, Shane Richards, Elizabeth Ainsbury, Kai Rothkamm, Simon Bouffler, Roy A. Quinlan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of γH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (γH2AX, 53BP1 and RAD51) in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-2′-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy. After 10 months, the lens aspect ratio was also altered, an indicator of the consequences of the altered cell proliferation and cell density changes. A best-fit model demonstrated a dose-response peak at 500 mGy. These data identify specific nonlinear biological responses to low (less than 1000 mGy) dose IR-induced DNA damage in the lens epithelium.

Original languageEnglish
Article number150011
JournalOpen Biology
Volume5
Issue number4
DOIs
Publication statusPublished - 29 Apr 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors. Published by the Royal Society.

Keywords

  • Cyclin D1
  • DNA DSB
  • Eye lens
  • Ionizing radiation
  • Non-linear effect
  • γH2AX

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