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    Modelling chromosomal aberration induction by ionising radiation: the influence of interphase chromosome architecture.

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    Several advances have been achieved in the knowledge of nuclear architecture and functions during the last decade, thus allowing the identification of interphase chromosome territories and sub-chromosomal domains (e.g. arm and band domains). This is an important step in the study of radiation-induced chromosome aberrations; indeed, the coupling between track-structure simulations and reliable descriptions of the geometrical properties of the target is one of the main tasks in modelling aberration induction by radiation, since it allows one to clarify the role of the initial positioning of two DNA lesions in determining their interaction probability. In the present paper, the main recent findings on nuclear and chromosomal architecture are summarised. A few examples of models based on different descriptions of interphase chromosome organisation (random-walk models, domain models and static models) are presented, focussing on how the approach adopted in modelling the target nuclei and chromosomes can influence the simulation of chromosomal aberration yields. Each model is discussed by taking into account available experimental data on chromosome aberration induction and/or interphase chromatin organisation. Preliminary results from a mechanistic model based on a coupling between radiation trackstructure features and explicitly-modelled, non-overlapping chromosome territories are presented

    Mechanistic and phenomenological models for the estimate of radiation-induced biological damage. Physica Medica 17, 3-12.

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    Different techniques for modelling the radiation action on biological targets are analysed, focussing the attention on phenomenological and mechanistic approaches. Phenomenological models allow practical applications (typically in radioprotection and radiotherapy) and are characterised by descriptive features aimed to organise the experimental observations within a formal structure. Mechanistic models are used in basic research and are aimed to reach a better understanding of the physical, chemical and biological processes that, from the initial energy depositions, lead to biological damage. Many different orders of magnitude are involved, both at a spatial level (from atomic dimensions to cellular and organ dimensions) and at a temporal level (from the 10(-15) s of the physical interactions to the hours, and possibly years, of the biological processes). The following aspects are treated: track structure; DNA damage; chromosome aberrations; cell inactivation; low doses and mixed fields. The attention focuses on the comparison between simulations and experiments, the comparison between mechanistic and phenomenological approaches, the determination of the model parameters (in particular on the uncertainties and correlations) and the role of the models in radioprotection and radiotherapy applications

    Nuclear architecture and radiation-induced chromosome aberrations: models and simulations.

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    Knowledge of radiation track structure and its interaction with biological targets is a fundamental starting point in understanding the mechanisms underlying the induction of biological damage. In this context Monte Carlo codes are a powerful tool of investigation, allowing one to simulate both track structure and the features of the target(s) of interest at different scales, from nanometres (linear dimensions of DNA) to micrometres (linear dimensions of human cell nuclei and interphase chromosome territories). In the light of recent experimental findings on nuclear architecture, different approaches in modelling chromosome structure and aberration induction are discussed. In particular, a model is presented in which chromosome territories were explicitly described as subnuclear regions and aberration induction was modelled by coupling the structure of the target with that of the radiation track. Comparisons between model predictions and experimental results from the literature are also reported
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