Differential effects of x-rays and high-energy 56Fe ions on human mesenchymal stem cells.
OBJECTIVE
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) (56)Fe ions on human mesenchymal stem cells (hMSC).


METHODS
A multi-functional comparison was carried out to investigate the differential effects of X-rays and (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 (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 (56)Fe ions, with more significant effects from (56)Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy (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
(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.
Kurpinski
Kyle
K
Department of Bioengineering, University of California-Berkeley, Berkeley, CA, USA.
Jang
Deok-Jin
DJ
Bhattacharya
Sanchita
S
Rydberg
Bjorn
B
Chu
Julia
J
So
Joanna
J
Wyrobek
Andy
A
Li
Song
S
Wang
Daojing
D
D000469:Alkaline Phosphatase / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism; D002453:Cell Cycle / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D003599:Cytoskeleton / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D016158:Genes, p53 / Q000528:radiation effects; D006801:Humans; D007501:Iron; D018499:Linear Energy Transfer; D059630:Mesenchymal Stem Cells / Q000502:physiology / Q000528:radiation effects*; D046228:Microarray Analysis / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010012:Osteogenesis; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D015398:Signal Transduction; D014965:X-Rays
D002130:Calcium Phosphates; D012333:RNA, Messenger; C020243:calcium phosphate; D007501:Iron; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase