Chromosome packing in cell nuclei: towards understanding of radiation-induced gene translocation frequency

Unlike biodosimetry of sparsely ionizing photons (X and gamma rays), radio-biology and biodosimetry of densely ionizing (characterized by high linear energy transfer) heavy ions are still relatively poorly developed domains of science, despite a growing role of hadron beams in cancer therapy and an increasing frequency of exposure of humans to cosmic radiation. The most radiosensitive cell structure is the DNA which is responsible for storing genetic information. Interaction of radiation with the DNA leads to the formation of different types of DNA damage, the most severe of which are DNA double-strand breaks (DSBs). Damage to the DNA activates repair processes and their performance may be significantly reduced or stopped if the resulting damage is densely localized (clustered) on the distances of the order of nanometers. Erratic DNA repair leads to changes in the DNA structure causing rearrangements of the genome (chromosome aberrations), possibly resulting in subsequent cell death or induction of cancer. Relating models of chromosome geometry and their spatial position in the nucleus to a characteristic pattern of energy deposition in the biological target by incident radiation (track structure) allows us to predict the frequency and distribution of DSBs, displacement of formed fragments, and probability of translocation of genetic material between pairs of chromosomes. In this work, we analyze results of the biophysical modeling of chromosome packing in the cell nucleus and confront them with cytogenetic experimental data evidenced by the former in vitro studies. In the quest for under-standing effects of interphase chromosome geometry on the induction and frequency of chromosome aberrations, we have evaluated two models of the DNA polymer packing within the cell nucleus and validated the predicted exchange of genome with experimental findings.