New tools for probing biological extremes of ionizing radiation

Abstract: Three different biological extremes of irradiation of living organisms, both human and animal, have been investigated and are presented in this thesis. Central to the thesis is the concept of bystander effects of ionizing radiation, i.e. biological responses in a cell that are not caused by that cell receiving a direct hit by ionizing radiation but by the fact that a neighbouring cell has been hit by ionizing radiation. The first extreme is represented by preparations for a single-ion hit facility, providing the opportunity to deliver very low doses, down to single ions, of irradiation with a proton microprobe. Such a facility is a very helpful tool when studying low-dose effects, such as bystander effects, in a well-defined and controlled manner. These preparations consisted of: 1) characterization of thin semiconductor detectors that could be used to detect single ions, and 2) fabrication of a patterned cell substrate, where cells can be guided to grow in small, separated islands. The second extreme is represented by low-dose experiments on human cells in the search for bystander effects of ionizing radiation. These biological experiments, where a collimated alpha particle source was used instead of a proton microprobe, were carried out on cells cultured in standard Petri dishes. The third and final extreme is represented by irradiation experiments carried out on an extremely radiation-tolerant animal, the tardigrade, illustrating the delivery of very high doses using a proton microprobe – this project being the opposite of the first and second extreme in a sense. These three projects have resulted in a possible new detector set-up, where a thin transmission detector has been shown to be suitable for use in a single-ion hit facility, and a patterned cell substrate that is easy and fast to fabricate and which is well-suited for irradiation experiments. Furthermore, a protein, alpha-1-microglobulin, has been shown to have cell-protection properties, minimizing the spread of cell death to bystander cells after alpha particle irradiation. Finally, the tolerance of the tardigrade to proton irradiation has been investigated for the first time, revealing that this animal is indeed extremely radiation tolerant.