Led by PD Dr. Christine Elisabeth Hellweg
The exposure to the space radiation environment remains a major limiting factor for human long-duration space missions and permanent presence in space habitats due to its high biological effectiveness and the difficulties to effectively shield the radiation. The working group Biodiagnostics develops and applies cellular test systems to monitor and understand the impact of space and environmental conditions (mostly radiation) on humans on a cellular and molecular level. It thereby attempts to understand the molecular mechanisms of the cellular response to space radiation in order to identify the pathways to disease in different target organs, to assess individual variations of radiation sensitivity and to find biomarkers of radiation exposure and individual sensitivity.
Cellular radiation response
Nuclear translocation of NF-κB, Image: DLR (CC-BY 3.0)
Cells respond actively to radiation exposure, starting with sensing of the inflicted DNA damage and initiation of repair. Changes in signal transduction and gene expression turn the switch towards cellular outcomes such as cell cycle arrest, cell death, premature differentiation or senescence. The work group has shown that heavy ions (as important component of space radiation) activate the Nuclear Factor κB (NF-κB) pathway which is involved in inflammatory responses with very high efficiency, resulting a specific cyto- and chemokine expression profile [1-3]. These early cellular radiation effects might pave the way to diseases such as cancer and degenerative alterations. Target organs for degenerative effects induced by galactic cosmic rays, especially the brain, the cardiovascular system and the eye lens, are in the focus of the radiobiological research.
Eye lens preparation (© Bikash Konda)
Factors influencing the radiation response
Besides the chronic space radiation exposure, astronauts experience a quite unique combination of possibly health-deteriorating environmental factors such as microgravity, noise, smell, disturbed circadian rhythm, increased carbon dioxide concentrations and decreased sleep quality. For exploration missions, the oxygen content and pressure of the atmosphere might be altered. The interaction of radiation exposure with these space environmental factors such as microgravity or changes in the atmospheric conditions might influence the cells’ capability to cope with radiation damage. The oxygen content of the tissue is recognized as a major modulator of the radiation sensitivity, with a decrease by a factor of three in absence of oxygen compared to normoxic conditions. Also, the fluid shift towards the head might modulate radiation effects on the brain and eye. Recently, it was observed that the body temperature of astronauts on ISS is increased. In this context, it has to be considered that in some cancer therapy regimens, hyperthermia is combined with radiotherapy in order to augment the tumor cell killing effect.
Culturing cells under hypoxia, Image: DLR (CC-BY 3.0)
Individual variations of radiation sensitivity
Human response to ionizing radiation is individual and variable. The heritability of various parameters of radiation sensitivity (chromosome aberrations, DNA damage response, cell cycle changes and cell death) is between 40-80%. Investigations of the individual radiation sensitivity are thought to provide the basis for personalized countermeasures against key environmental factors in long-term missions such as space radiation, and will also provide important results for use in terrestrial medicine. The first step in this research field is the development of innovative biomarkers for radiation sensitivity that can be determined in a blood sample.
Working with an oxygen mask, Image: DLR (CC-BY 3.0)
 Hellweg CE, Baumstark-Khan C, Schmitz C, Lau P, Meier MM, Testard I, Berger T, Reitz G (2011) Activation of the NF-κB pathway by heavy ion beams of different linear energy transfer. International Journal of Radiation Biology 87, 954-963.
 Hellweg CE, Spitta L, Koch K, Chishti AA, Henschenmacher B, Diegeler S, Konda B, Feles S, Schmitz C, Berger T, Baumstark-Khan C (2018) The Role of the Nuclear Factor κB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation. International Journal of Molecular Sciences, 19 (8): 2220.
 Chishti AA, Baumstark-Khan C, Koch K, Kolanus W, Feles S, Konda B, Azhar A, Spitta LF, Henschenmacher B, Diegeler S, Schmitz C, Hellweg CE (2018) Linear Energy Transfer Modulates Radiation-Induced NF-κB Activation and Expression of its Downstream Target Genes. Radiation Research, 189 (4): 354-370.