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

Abstract

Purpose: We studied the response of human embryonic stem cells (hESC) to the β-emitter ¹³¹I, which affects the entire cell and to the Auger electron emitter ¹²⁵I-deoxyuridine (¹²⁵I-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 ¹²⁵I-dU (5 × 10^?5 – 5 MBq/ml) and ¹³¹I-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 ¹²⁵I-dU and ¹³¹I treatments, whereas HaCaT cells expressed a much more pronounced response to ¹²⁵I-dU than to ¹³¹I. 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 ¹²⁵I-dU and ¹³¹I 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.