LABORATORI NAZIONALI DI LEGNARO
Chromosome aberrations are considered to be surrogate end points for many deleterious biological effects such as cell killing, mutagenesis and carcinogenesis. Different types of chromosome aberrations including complex chromosome rearrangements have been studied experimentally. A measurement of the rearrangements of chromosomes in human lymphocytes has been suggested as biological dosimeters for radiation exposure. It is generally believed that unfaithful rejoining between double strand breaks can lead to chromosome aberrations. These breaks and subsequent rejoining can be within a single chromosome (intra-) or between different chromosomes (inter-). What rule or rules govern this rejoining process? How far do the breaks have to be so that there is a reasonable probability of interaction between them? How does the faithful rejoining process compete with the faithful rejoining process? To what extent DSBs account for all the observed yield of chromosome aberrations? In order to answer these questions one needs to have a reliable and well tested theoretical model which will not only be able to reproduce experimental data at high doses but also predict results at low doses for all qualities of ionizing radiation. A theoretical model will be presented for evaluating radiation- induced chromosomal exchanges by explicitly taking into account inter-phase (G0 / G1) chromosome structure in terms of chromatin folding, nuclear organization of chromosomes, the production of double strand breaks (DSBs), and the subsequent rejoining in a faithful or unfaithful manner. Each of the 46 chromosomes for human cells (40 chromosomes for mouse cells) is modeled as a random polymer inside a spherical volume. The chromosome spheres are packed randomly inside a cell nucleus with an allowed overlap controlled by a parameter omega. The rejoining of DSBs is determined by a Monte Carlo procedure using a Gaussian proximity function with an interaction range parameter . This model has been used to calculate yields of translocations and dicentrics for different types of human cells exposed to different qualities of radiation. Theoretical calculations have detectable sensitivity down to a change of 1bp and we have evaluated the effects of different resolution limits on simple as well as complex aberrations and to what extent experimental data are underestimating the yield of aberrations.

DATA: 22-06-2005