CHROMATIN STRUCTURE AND CHROMOSOME-ABERRATIONS - MODELING OF DAMAGE-INDUCED BY ISOTROPIC AND LOCALIZED IRRADIATION

Various models for the nuclear architecture in interphase cell nuclei have been presented, proposing a territorial or a non-territorial orga nization of chromosomes. To better understand the correlation between nuclear architecture and the formation of chromosomal aberrations, we applied computer simulations to model the extent of radiation induced chromosome damage under certain geometrical constraints. For this purp ose, chromosomes were described by different models, which approximate the chromatin fiber by a polymer chain, folded in different ways. Cor responding to the different condensation levels, a territorial or a no n-territorial organization of chromosomes was obtained. To determine t he relative frequencies of radiation induced damage, the effects of is otropic ionizing radiation and of a focused laser UV-beam were studied . For isotropic ionizing radiation, the calculated translocation frequ encies showed no differences between territorial and non-territorial m odels except for one special case. For localized irradiation, the resu lts of both organizations were clearly different, with respect to the total number of damaged chromosomes per cell. The predictions agreed w ell with the experimental data available. (C) 1998 Elsevier Science B. V. All rights reserved.