title: Cellular response on Auger- and Beta-emitting nuclides: human embryonic stem cells (hESC) vs. keratinocytes.
abstract: OBJECTIVE
  We studied the response of human embryonic stem cells (hESC) to the β-emitter (131)I, which affects the entire cell and to the Auger electron emitter (125)I-deoxyuridine ((125)I-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 (125)I-dU (5 × 10(-5) - 5 MBq/ml) and (131)I-iodide (5 × 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 (125)I-dU and (131)I treatments, whereas HaCaT cells expressed a much more pronounced response to (125)I-dU than to (131)I. 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 (125)I-dU and (131)I 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.
authors.affiliation: Department of Nuclear Medicine, University of Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Sudbrock
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Pomplun
authors.forename: Ralf
authors.initials: R
authors.lastname: Kriehuber
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
authors.forename: Matthias
authors.initials: M
authors.lastname: Matzkies
authors.forename: Alexander
authors.initials: A
authors.lastname: Dellweg
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
authors.forename: Stefan
authors.initials: S
authors.lastname: Arnhold
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Royer
authors.forename: Harald
authors.initials: H
authors.lastname: Schicha
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Klaus
authors.initials: K
authors.lastname: Schomäcker
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded / Q000528:radiation effects; D053938:DNA Fragmentation / Q000528:radiation effects; D003857:Deoxyuridine / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D006801:Humans; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D014158:Transcription, Genetic / Q000528:radiation effects; D059467:Transcriptome / Q000528:radiation effects
chemical_list: D007457:Iodine Radioisotopes; D003857:Deoxyuridine