title: Effects of low doses of ionizing radiation exposures on stress-responsive gene expression in human embryonic stem cells.
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.
authors.affiliation: Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, 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, 9000 Rockville Pike, Bethesda, MD 20892, USA. rneumann@mail.nih.gov.
authors.forename: Ronald
authors.initials: R
authors.lastname: Neumann
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D000097642:GADD45 Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C438378:BBC3 protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins