Cellular response on Auger- and Beta-emitting nuclides: human embryonic stem cells (hESC) vs. keratinocytes.

Fischer, Thomas; Sudbrock, Ferdinand; Pomplun, Ekkehard; Kriehuber, Ralf; Winkler, Johannes; Matzkies, Matthias; Dellweg, Alexander; Dietlein, Markus; Arnhold, Stefan; Royer, Hans-Dieter; Schicha, Harald; Hescheler, Jürgen; Schomäcker, Klaus

PURPOSE 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.