A few examples of models of chromosome aberration induction are summarised and discussed on the basis of the three main theories of aberration formation, that is “breakage-and-reunion”, “exchange” and “one-hit”. A model and code developed at the Universities of Milan and Pavia is then presented in detail. The model provides dose-response curves for different aberration types (dicentrics, translocations, rings, complex exchanges and deletions) induced in human lymphocytes by gamma rays, protons and alpha particles of different energies, both as monochromatic fields and as mixed fields. The main assumptions are that only clustered - and thus severe - DNA breaks ("Complex Lesions", CL) can participate in the production of aberrations, and that only break free-ends in neighbouring chromosome territories can interact and form exchanges. The yields of CLs induced by the various radiation types of interest are taken from a previous modelling work. These lesions are distributed within a sphere representing the cell nucleus according to the radiation track structure, e.g. randomly for gamma rays and along straight lines for light ions. Interphase chromosome territories are explicitly simulated and configurations are obtained in which each chromosome occupies an intranuclear domain with volume proportional to its DNA content. In order to allow direct comparisons with experimental data, small fragments can be neglected since usually they cannot be detected in experiments. The presence of a background level of aberrations is also taken into account. The results of the simulations are in good agreement with experimental dose-response curves available in the literature, that provides a validation of the model both in terms of the adopted assumptions and in terms of the simulation techniques. To address the question of “true” incompleteness, simulations were also run in which all fragments were assumed to be visible.

Models of chromosome aberration induction: an example based on radiation track structure

BALLARINI, FRANCESCA;OTTOLENGHI, ANDREA DAVIDE
2004-01-01

Abstract

A few examples of models of chromosome aberration induction are summarised and discussed on the basis of the three main theories of aberration formation, that is “breakage-and-reunion”, “exchange” and “one-hit”. A model and code developed at the Universities of Milan and Pavia is then presented in detail. The model provides dose-response curves for different aberration types (dicentrics, translocations, rings, complex exchanges and deletions) induced in human lymphocytes by gamma rays, protons and alpha particles of different energies, both as monochromatic fields and as mixed fields. The main assumptions are that only clustered - and thus severe - DNA breaks ("Complex Lesions", CL) can participate in the production of aberrations, and that only break free-ends in neighbouring chromosome territories can interact and form exchanges. The yields of CLs induced by the various radiation types of interest are taken from a previous modelling work. These lesions are distributed within a sphere representing the cell nucleus according to the radiation track structure, e.g. randomly for gamma rays and along straight lines for light ions. Interphase chromosome territories are explicitly simulated and configurations are obtained in which each chromosome occupies an intranuclear domain with volume proportional to its DNA content. In order to allow direct comparisons with experimental data, small fragments can be neglected since usually they cannot be detected in experiments. The presence of a background level of aberrations is also taken into account. The results of the simulations are in good agreement with experimental dose-response curves available in the literature, that provides a validation of the model both in terms of the adopted assumptions and in terms of the simulation techniques. To address the question of “true” incompleteness, simulations were also run in which all fragments were assumed to be visible.
2004
Biochemistry & Biophysics focuses on the structure and chemistry of biomolecules and covers all aspects of basic biochemistry/biophysics, including molecular structure, enzyme kinetics and protein-protein interaction; this category also contains cross-disciplinary resources focused on a specific class of biological molecules, e.g., nucleic acids, steroids, magnesium, growth factors, free radicals, bio-membranes, and peptides. Excluded are resources dealing with the application of biochemical techniques to specific topics listed elsewhere in CC/LS. Resources with a strong emphasis on the integration of biochemical pathways (such as signal transduction or molecular motors) at the cellular level are placed in the Cell & Developmental Biology category.
Sì, ma tipo non specificato
Inglese
Internazionale
STAMPA
104
149
156
IONIZING RADIATION DAMAGE; CHROMOSOME ABERRATIONS; THEORETICAL MODELS; MONTE CARLO SIMULATIONS; TRACK STRUCTURE
2
info:eu-repo/semantics/article
262
Ballarini, Francesca; Ottolenghi, ANDREA DAVIDE
1 Contributo su Rivista::1.1 Articolo in rivista
none
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/120203
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