MIMO-BRAGG | ||
MIsura e MOdellizzazione di danno citogenetico lungo la curva di BRAGG di ioni accelerati |
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STATE-OF-THE-ART
Ionising radiation is unique among all the environmental and man-made mutagen and carcinogen agents. The damage it induces as a result of a complex cascade of biochemical processes at the molecular and cellular level is a direct consequence of the peculiar mode with which the energy is released along the radiation path. Complex DNA lesions encompassing breaks and base damage are extremely difficult to repair and result from the typical ionisation spurs and clusters occurring mainly along the track of densely ionizing (high LET) radiation. Such lesions hamper correct repair and, since they can be more effectively induced by charged particles, they are believed to be the reason for the higher Relative Biological Effectiveness (RBE) of particle-type radiation compared to photons [1]. However, there still lacks a thorough comprehension of the radiobiological effects due to the exposure to this type of radiation, whose precise elucidation at both the mechanistic and experimental level is essential for reliably estimating the health risks, especially as far as long-term and delayed effects are concerned [2-5]. Traditionally, the differences in RBEs found between different radiation qualities have been studied as a function of the radiation LET. However, radiation effectiveness is critically determined by the configuration of all the ionisation events caused by primary and secondary particles, that is the ion track structure [6,7]. At high LET, energy is deposited differently according to the ion mass and initial energy. This means that its biological effectiveness may differ for the same absorbed energy (dose), hence the RBE is not constant along the ion track [8,9]. Since the track diameter is proportional to the LET but it depends on the particle energy and, for a given energy, on the particle Z, the ionisation density will be different between different ions despite having the same LET. In hadrontherapy, for example, this justifies the preference of carbon ions over protons in that the former exhibit a higher RBE at the same LET values but also explains why the RBE does vary across the volume treated with a carbon ion beam. Therefore, the continuous change in the ionisation density as the ion slows down translates into a continuously changing radiobiological effectiveness along the ion track. Therefore, if a precise interpretation of the observed results and of the relative models for charged particle radiation has to be achieved, the different track structure between ions must be taken into account (fig.1).
Most of existing radiobiological data are on lethal effects in tumour cells, mainly from the peak portion of the Bragg curve. Sub-lethal damage, which is more likely to arise from the entrance region of the curve and is more relevant for the stability of the genome of the normal cells involved as well as for the proper functions at the tissue level, has been essentially overlooked [10-13]. Knowledge of the effectiveness with a given ion causes such late-occurring damage along the whole Bragg curve, would allow to construct a biological mapping of the physical curve and to determine how such damage can differ, for a given LET, between different ions, thereby potentially improving current exposure guidelines in radiation protection and treatment plans in hadrontherapy [14]. Normal human cell lines will be used to study the in vitro induction of cytogenetic damage of relevance for late-occurring effects such as cancer and normal tissue loss of function. In particular, chromosomal aberrations, micronuclei, DNA damage foci formation and cellular senescence will be assayed in cells exposed to accelerated beams of 62 MeV/n 16O, 19F and 20Ne at various positions along the Bragg curve. Experimental data will be compared with those obtained by the collaborating experiment DNA BRAGG (CCRCB, Queen University Belfast, UK) with 12C ions and be used to implement existing codes for chromosome aberration formation following high LET radiation as well as Geant 4-based simulations for LET calculations developed by the collaboration with the INFN-MC_Geant4 experiment (LNS-INFN).
References
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Realized by Carla Maiorino, 2012 |