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

Markiewicz, Ewa and Barnard, Stephen and Haines, Jackie and Coster, Margaret and Geel, Orry van and Wu, Weiju and Richards, Shane and Ainsbury, Elizabeth and Rothkamm, Kai and Bouffler, Simon and Quinlan, Roy A. (2015) 'Nonlinear ionizing radiation-induced changes in eye lens cell proliferation, cyclin D1 expression and lens shape.', Open biology., 5 . p. 150011.


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 central 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 gH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (gH2AX, 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-20-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.

Item Type:Article
Keywords:Ionizing radiation, Eye lens, Cyclin D1, gH2AX, DNA DSB, Non-linear effect
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Available under License - Creative Commons Attribution.
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Publisher statement:© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License, which permits unrestricted use, provided the original author and source are credited.
Date accepted:31 March 2015
Date deposited:29 April 2015
Date of first online publication:29 April 2015
Date first made open access:No date available

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