Rearrangement of human cell homologous chromosome domains in response to ionizing radiation

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Abstract
Chromosomes are located within the interphase nucleus in regions called domains. Using fluorescence in situ hybridization with whole chromosome paints, a pair of homologous chromosomes can be visualized as two discrete domains and their relative spatial location determined. This study examines the effects of an ionizing radiation exposure on the relative spatial location of chromosome 7 and 21 domains in human skin fibroblasts and lung endothelial cells. The distance between homologous chromosome domains was assessed for each nucleus, before and after exposure to ionizing radiation, using conventional epifluorescence and confocal laser scanning microscopy. Results from conventional microscopy indicated that homologous chromosome domains were re-positioned closer to each other within interphase nuclei after exposure to radiation. Analysis of three-dimensional data obtained from confocal microscopy confirmed these results. In control cells, and in cells examined immediately after irradiation, 66.2% 2.1% of the homologous chromosome 21 domains within endothelial cell nuclei were located greater than 4.0 mu m apart (33.8% 1.9% were less than 4.0 mu m apart). However, when cells were examined 2 h after a 4.0 Gy gamma-ray exposure, only 30.5% 2.1% of the homologous chromosome domains were greater than 4.0 mu m apart (69.5% 2.1% were less than 4.0 mu m apart). Similar results were obtained for chromosomes 7 and 21 in skin fibroblast nuclei. The results indicate that homologous chromosome domains rearranged and became closer together within the interphase nuclei in response to ionizing radiation. The exact mechanism of this response is unknown, but it may be related to DNA repair processes. It is speculated that chromosome domains are re-positioned to permit repair of radiation-induced DNA damage.