For risk assessment and countermeasure development, pathways playing important roles in radiation induced cancerogenesis have 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 53 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.
NF-κB also enhances the expression of degradative enzymes, supporting the idea that it makes a major contribution to tumor progression.
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 the NF-κB and the p53 pathway. Their effect on the biological outcome (alterations in gene expression, cell cycle arrest, apoptosis and other types of cell death, DNA repair) will be analyzed by microarrays, real-time quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR), translocation vectors with fluorescent marker proteins and immunofluorescence (confocal microscopy), 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
Dr. Christine E. Hellweg++49 2203 601 3243Email: Christine Hellweg
Prof. Dr. Jürgen Dohmen (University of Cologne)++49-221-470-4862
Prof. Waldemar Kolanus (University of Bonn)++49-228-73-62790
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