Gene expression profile of human cells in response to simulated space radiation
- Paper number
IAC-10.A1.4.10
- Author
Dr. Christine Hellweg, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Coauthor
Dr. Christa Baumstark-Khan, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Coauthor
Mrs. Rebecca Ruland, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Coauthor
Mrs. Claudia Schmitz, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Coauthor
Dr. Patrick Lau, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Coauthor
Dr. Isabelle Testard, CEA, France
- Coauthor
Dr. Günther Reitz, Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR), Germany
- Year
2010
- Abstract
Space radiation is a potentially limiting factor for manned long term orbital and interplanetary missions. Understanding of the cellular and molecular processes underlying cell death and transformation related events by space radiation may allow better risk estimation and development of appropriate countermeasures. The pathway leading to activation of the transcription factor nuclear factor $\kappa$B (NF-$\kappa$B) and increased transcription of its target genes might modulate the cellular radiation response. Previous studies suggest a linear energy transfer (LET) dependency of NF-$\kappa$B activation: high LET radiation activates NF-$\kappa$B more efficiently than low LET radiation. In this work, the relative expressions of several NF-$\kappa$B regulated genes (Gadd45$\beta$, NFKBIA encoding the NF-$\kappa$B inhibitor I$\kappa$B$\alpha$, and the anti-apoptotic genes XIAP, bcl-2, and bcl-xL) were examined by quantitative real-time Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). Human embryonic cells with neuronal differentiation potential (HEK/293) were exposed to accelerated heavy ions or to X-rays (200 kV) or incubated in presence of the strong NF-$\kappa$B activator tumor necrosis factor $\alpha$ (TNF-$\alpha$). Target gene expression data were normalized to the expression index of several unregulated reference genes (B2M, GAPDH, PBGD, HPRT). NFKBIA expression is enhanced for 24 h after TNF-$\alpha$ treatment, while Gadd45$\beta$ expression was only temporarily up-regulated. High doses of X-rays (8 and 16 Gy) and of C-13 ions (75 MeV/n, LET 33 keV/$\mu$µm, 4.7 Gy) up-regulate NFKBIA and Gadd45$\beta$ expression temporarily. C-13 ions with higher LET (35 MeV/n, 73 keV/$\mu$µm) enhance NFKBIA expression already after 1 Gy, and a passing up-regulation of Bcl-2, bcl-xL and XIAP expression was observed 2 h after 0.5 Gy. Ne-20 (95 MeV/A, 80 keV/$\mu$µm) and Ar-36 ions (95 MeV/A, 271 keV/$\mu$µm) were the strongest inducers of Gadd45$\beta$, NFKBIA, and XIAP with doses from 0.5 to 3.8 Gy. Ni-58 (75 MeV/A, 906 keV/$\mu$µm) and Pb-208 ion exposure (29 MeV/A, 9764 keV/$\mu$µm) reduced the expression of Gadd45$\beta$. NFKBIA expression was enhanced after Ni-58 ion exposure, but down-regulated after Pb-208 ion exposure. Bcl-2 and Bcl-xL were mostly unaffected by the tested irradiation conditions or only transitorily up-regulated. In conclusion, genes involved in cell cycle regulation (Gadd45$\beta$), in inhibition of apoptosis (XIAP, bcl-2, and bcl-xL) and in control of the NF-$\kappa$B pathway (NFKBIA) show a differentiated expression profile after exposure of human cells to heavy ions of different LET. This might be a step towards understanding of the previously observed LET dependency of cell survival and cell cycle arrest.
- Abstract document
- Manuscript document
IAC-10.A1.4.10.pdf (🔒 authorized access only).
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