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Int. J. Mol. Sci. 2014, 15(1), 588-604; doi:10.3390/ijms15010588
Article

Effects of Low Doses of Ionizing Radiation Exposures on Stress-Responsive Gene Expression in Human Embryonic Stem Cells

*  and
Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
* Author to whom correspondence should be addressed.
Received: 1 November 2013 / Revised: 25 December 2013 / Accepted: 26 December 2013 / Published: 6 January 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

There is a great deal of uncertainty on how low (≤0.1 Gy) doses of ionizing radiation (IR) affect human cells, partly due to a lack of suitable experimental model systems for such studies. The uncertainties arising from low-dose IR human data undermine practical societal needs to predict health risks emerging from diagnostic medical tests’ radiation, natural background radiation, and environmental radiological accidents. To eliminate a variability associated with remarkable differences in radioresponses of hundreds of differentiated cell types, we established a novel, human embryonic stem cell (hESC)-based model to examine the radiobiological effects in human cells. Our aim is to comprehensively elucidate the gene expression changes in a panel of various hESC lines following low IR doses of 0.01; 0.05; 0.1 Gy; and, as a reference, relatively high dose of 1 Gy of IR. Here, we examined the dynamics of transcriptional changes of well-established IR-responsive set of genes, including CDKN1A, GADD45A, etc. at 2 and 16 h post-IR, representing “early” and “late” radioresponses of hESCs. Our findings suggest the temporal- and hESC line-dependence of stress gene radioresponses with no statistically significant evidence for a linear dose-response relationship within the lowest doses of IR exposures.
Keywords: human embryonic stem cells; ionizing radiation; low dose exposures; gene expression changes human embryonic stem cells; ionizing radiation; low dose exposures; gene expression changes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sokolov, M.; Neumann, R. Effects of Low Doses of Ionizing Radiation Exposures on Stress-Responsive Gene Expression in Human Embryonic Stem Cells. Int. J. Mol. Sci. 2014, 15, 588-604.

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