Differential Effects of X-Rays and High-Energy {sup 56}Fe Ions on Human Mesenchymal Stem Cells
- Department of Bioengineering, University of California-Berkeley, Berkeley, CA (United States)
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States)
Purpose: Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) {sup 56}Fe ions on human mesenchymal stem cells (hMSC). Methods and Materials: A multi-functional comparison was carried out to investigate the differential effects of X-rays and {sup 56}Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis. Results: X-rays and {sup 56}Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and {sup 56}Fe ions, with more significant effects from {sup 56}Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy {sup 56}Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter. Conclusions: {sup 56}Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.
- OSTI ID:
- 21172641
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 73, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2008.10.002; PII: S0360-3016(08)03527-X; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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