Cellular Radiation Effects and Bystander Effects
When comparing terrestrial low-linear energy transfer (LET) radiation (X-rays or g-rays) to high-LET space radiation qualities (heavy ions and secondary neutrons), differences in the patterns of energy deposition in biomolecules, cells and tissues occur, which on cellular level are only poorly understood and on organ level information is still incomplete.
Exposure to ionizing radiation modifies the cellular division processes as well as other cell functions required for healthy living organisms. Cells have the ability to repair themselves; when that repair is successful, the tissues and organisms return to their normal state. When the repair is not successful, cells may die, mutate or differentiate along their lineage.
If a sufficiently large number of cells are killed, tissue integrity and function may be impaired, as occurs in acute radiation effects. Repair may be successful from the point of view of cell survival, but may contain latent errors that only manifest in subsequent generations of dividing cells. Such errors may contribute to radiation induced cancerogenesis and cataractogenesis.
The active cellular response to radiation exposure involves triggering of many signaling pathways and the activation of transcription factors. For risk assessment and countermeasure development, the role of such pathways in radiation induced cancerogenesis and cataractogenesis has to be understood.
In view of its tumor-promoting capacity, Nuclear Factor κB (NF-κB) is an important factor involved in the modulation of environment-induced gene expression, especially in the interplay of the pro-apoptotic p53 pathway and the pro-survival NF-κB pathway after low and high dose radiation. The transcription factor p53 plays a central role as a principal regulator of the G1 cell cycle checkpoint in maintaining the integrity of genome after exposure to DNA-damaging agents, thereby acting as a tumor suppressor.
p53 protein regulates the expression of specific genes involved in growth regulation and apoptosis, while NF-κB regulates the expression of specific anti-apoptotic genes involved in innate and adaptive immunity and in oncogenesis. Activation of the NF-κB pathway gives transformed cells a growth and survival advantage and further renders tumor cells resistant to chemo- and radiation therapy.
At the Institute of Aerospace Medicine, the biological effects of cosmic radiation are analyzed by several approaches: Different radiation qualities (sparsely ionizing X-rays, densely ionizing a-particles and accelerated heavy ions as well as neutrons) are supposed to have different induction potencies for stress-induced pathways. Their effect on the biological outcome (alterations in gene expression, cell cycle arrest, apoptosis and other types of cell death, DNA repair) are analyzed e.g. by microarrays, real-time quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR), translocation vectors with fluorescent marker proteins and immunofluorescence (confocal microscopy), promoter-reporter vectors, pulsed field gel electrophoresis, inhibitor and RNA interference studies, apoptosis assays and flow cytometric cell cycle analysis.
Dr. Christa Baumstark-Khan++49 2203 601 3140Email: Christa Baumstark-Khan
Prof. Dr. Jürgen Dohmen (University of Cologne)++49 221 470 4862
Dr. Christine E. Hellweg++49 2203 601 3243Email: Christine Hellweg
Prof. Waldemar Kolanus(University of Bonn)++49 228 73 62790
PD Dr. rer. nat. Alfred Wegener(University of Bonn)++49 228 287-15625
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