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

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posted on 2023-05-19, 07:44 authored by Markiewicz, E, Barnard, S, Haines, J, Coster, M, van Geel, O, Wu, W, Shane RichardsShane Richards, Ainsbury, E, Rothkamm, K, Bouffler, S, Quinlan, RA
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.

History

Publication title

Open Biology

Volume

5

Article number

150011

Number

150011

Pagination

1-14

ISSN

2046-2441

Department/School

School of Natural Sciences

Publisher

The Royal Society Publishing

Place of publication

United Kingdom

Rights statement

Copyright 2015 The Authors Copyright 2016 Doblin et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0

Repository Status

  • Open

Socio-economic Objectives

Expanding knowledge in the health sciences

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