Universität zu Köln

Fischer, Thomas, Sudbrock, Ferdinand, Pomplun, Ekkehard, Kriehuber, Ralf ORCID: 0000-0002-6657-4491, Winkler, Johannes, Matzkies, Matthias, Dellweg, Alexander, Dietlein, Markus, Arnhold, Stefan, Royer, Hans-Dieter, Schicha, Harald, Hescheler, Juergen and Schomaecker, Klaus (2012). Cellular response on Auger- and Beta-emitting nuclides: Human embryonic stem cells (hESC) vs. keratinocytes. Int. J. Radiat. Biol., 88 (12). S. 961 - 972. ABINGDON: TAYLOR & FRANCIS LTD. ISSN 1362-3095

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Abstract

Purpose: We studied the response of human embryonic stem cells (hESC) to the beta-emitter I-131, which affects the entire cell and to the Auger electron emitter I-125-deoxyuridine (I-125-dU), primarily affecting the deoxyribonuleic acid (DNA). The effects were also studied in keratinocytes as a prototype for somatic cells. Methods: HESC (H1) and human keratinocytes (HaCaT, human) were exposed to I-125-dU (5 x 10(-5) - 5 MBq/ml) and I-131-iodide (5 x 10(-5) - 12.5 MBq/ml) and apoptosis was measured by DNA-fragmentation. Cell morphology was studied by light microscopy and electron microscopy. Transcriptional profiling was done on the Agilent oligonucleotide microarray platform. Results : Auger-process induced no apoptosis but a strong transcriptional response in hESC. In contrast, HaCaT cells showed a pronounced induction of apoptosis but only a moderate transcriptional response. Transcriptional response of hESC was similar after I-125-dU and I-131 treatments, whereas HaCaT cells expressed a much more pronounced response to I-125-dU than to I-131. A striking radiation-induced down-regulation of pluripotency genes was observed in hESC whereas in keratinocytes the enriched gene annotations were related primarily to apoptosis, cell division and proliferation. Conclusions : Human embryonic stem cells respond to ionizing radiation by I-125-dU and I-131 in a different way compared to keratinocytes. Transcriptional response and gene expression appear to facilitate an escape from programmed cell death by striking a new path which probably leads to cell differentiation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fischer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Sudbrock, Ferdinand UNSPECIFIED UNSPECIFIED UNSPECIFIED Pomplun, Ekkehard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kriehuber, Ralf UNSPECIFIED orcid.org/0000-0002-6657-4491 UNSPECIFIED Winkler, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Matzkies, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Dellweg, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietlein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnhold, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Royer, Hans-Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schicha, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schomaecker, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-477505
DOI:	10.3109/09553002.2012.683510
Journal or Publication Title:	Int. J. Radiat. Biol.
Volume:	88
Number:	12
Page Range:	S. 961 - 972
Date:	2012
Publisher:	TAYLOR & FRANCIS LTD
Place of Publication:	ABINGDON
ISSN:	1362-3095
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IONIZING-RADIATION; LOW-LET; DIFFERENTIATION; CYCLE; PLURIPOTENCY; APOPTOSIS; P53; ACTIVATION; EXPRESSION; PROTECTION Multiple languages Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47750