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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 Molecular Toxicology)
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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 (CC BY 3.0).
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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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