In a low-dose field of γ-rays, such as that normally experienced on Earth due to background radiation, each human cell is traversed by very few electrons, which hence produce little damage. However, for energetic heavy ions, the situation is different. A low dose, such as the one experienced in a manned mission to the International Space Station or the Moon [1
], corresponds to only a few tracks, but each track can affect a whole tissue or organ, and each cell that is found in the path of the ion. The central part of the track, where most of the energy is deposited, has a radial extension of only a few nanometers, while a lower energy is deposited at a larger distance by energetic δ-rays. Thus, each heavy ion will produce a nanochannel in neighboring cells in a tissue or organ, a situation that makes the concept of low dose itself flawed. Although the concept of a “microlesion” induced by heavy ions in space was already acknowledged long ago [2
], there is a lack of experimental models for testing the hypothesis that they represent a distinct, unique type of damage at the tissue level. Moreover, Monte Carlo codes should be able to simulate the damage at the micrometer and even nanometer level, basing on the stochastic energy deposition pattern. One problem associated with the formation of nanolesions is the nonuniform structure of the target, i.e., of the cell nucleus [3
]. In fact, the compact heterochromatin provides a different environment compared to the transcriptionally competent euchromatin, and it had been proposed that heterochromatin was “refractory” to repair proteins [4
]. We have investigated in detail the structure of nanolesions, their formation and movement in the cell nucleus, using live cell microscopy and immunohistochemistry. Stimulated by the differences in repair kinetics and movement of the tracks in eu- and heterochromatin, we have further analyzed the histone modifications (particularly acetylation) along heavy-ion nanolesions. We have also started a full-genome deep-sequencing approach to correlate the microscopy data with the cellular response. In principle, the nanolesion structure can be predicted by accurate Monte Carlo simulations of the energy deposition by the projectile and of the target structure. We used the Monte Carlo model for heavy-ion therapy (MCHIT) code [5
] to simulate the energy deposition to micrometer-sized objects, e.g., cell nuclei, and compared the results to microdosimetric spectra previously measured [6
]. To further describe the nanometer region, the GSI track structure Monte Carlo code TRAX [7
], whose purpose is to properly describe the creation and transport of low energy electrons, has been extended to describe inhomogeneous targets.