Calaciran: A Dispute Settlement Mechanism for International Space Law
- Paper number
IAC-05-E6.4.06
- Author
Ms. Gérardine Meishan Goh, University of Cologne, Germany
- Year
2005
- Abstract
Radiation is a potentially limiting factor for long term orbital and interplanetary missions. Long-term exposure to galactic cosmic rays may shorten the healthy life-span after return to Earth due to cancer induction. During the mission, a solar flare can be life threatening as high radiation doses provoke cell death in vitally important tissues. For better risk estimation and development of appropriate countermeasures, the study of the cellular radiation response is necessary. Exposure of human cells to ionising radiation can provoke different types of cell death. The loss of clonogenic survival is generally measured using the colony forming ability (CFA) test. It reflects the capacity of irradiated cells to divide and form macro-colonies. Therefore, cell cycle arrest and different types of cell death, such as apoptosis, necrosis, mitotic catastrophe, cellular senescence and premature differentiation, can influence the results. Here, the contribution of apoptosis and cell cycle arrest to the reduced colony forming ability after irradiation was analysed. Human embryonic kidney (HEK/293) cells were exposed to different radiation qualities: sparsely ionising radiation (150 kV X-rays) and densely ionising radiation (high LET α-particles, accelerated argon and carbon ions). The lung carcinoma cell line A549 and Jurkat cells were exposed to X-rays for comparison. Cellular survival was measured using the CFA tests; cell cycle arrest was followed by flow cytometry of propidium iodide stained cells. Apoptotic cells were detected using a Phycoerythrin-coupled antibody against active Caspase 3. Exposure to X-rays resulted in typical shouldered survival curves indicating cellular DNA damage repair capacity. High-LET radiation results in purely exponential survival curves. The cell killing potential increases with LET up to 230 keV/µm. Exposure to all radiation qualities resulted in a G2 arrest, which extent and duration was dose-dependent. At higher fluences, the G2 arrest was not resolved 72 hours after irradiation. Caspase 3 activation as indicator of apoptosis was not significantly increased 6 and 24 hours after X-irradiation with doses up to 8 Gy in HEK and A549 cells. Jurkat cells underwent dose-dependent X-ray induced apoptotic cell death, which reached a maximum at 4 Gy. The results indicate that Caspase 3-dependent cell death in response to ionizing radiation plays a significant role for Jurkat cells. In the examined human epithelial cell lines HEK and A549, other mechanisms of cell death and the cell cycle arrest contribute to the reduced colony forming ability observed after exposure to different radiation qualities. As an antiapoptotic factor, if activated in human cells by exposure to components of cosmic rays, the transcription factor nuclear factor κB (NF-κB) could influence the cancer risk of astronauts exposed to cosmic radiation and improve cellular survival after exposure to high radiation doses. In previous studies, the activation of this transcription factor by heavy ions was shown (Radiat. Res. 164: 527-530, 2005). Results from exposure of HEK cells to different ion beams (36Ar, 95 MeV/u, LET 232 keV/?m, 13C, 75 MeV/u, LET 30 keV/µm, and 35 MeV/u, LET 70 keV/µm) or to X-rays suggest an LET dependency of NF-κB activation: high LET radiation activates NF-κB - dependent on initial nuclear DNA damage followed by cytoplasmic signalling events – more efficiently than low LET radiation. These results suggest a role of the NF-κB pathway as modulator of the radiation response. Therefore, regulation of this pathway may allow developing effective countermeasures for acute and late effects of radiation exposure during long-term space missions.
- Abstract document