title: Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure.
abstract: The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses.
authors.affiliation: Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. sokolovm@mail.nih.gov.
authors.forename: Mykyta
authors.initials: M
authors.lastname: Sokolov
authors.affiliation: Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. van.nguyen3@nih.gov.
authors.forename: Van
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. rneumann@mail.nih.gov.
authors.forename: Ronald
authors.initials: R
authors.lastname: Neumann
mesh_terms: D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D015894:Genome, Human; D006801:Humans; D011839:Radiation, Ionizing; D059467:Transcriptome / Q000528:radiation effects*
keywords: DNA microarray; human embryonic stem cell; ionizing radiation; low dose exposure; whole genome