Cellular progression towards the cancerous state frequently is associated with the loss of genomic integrity, expressing as variable genomic changes i.e. instability. The purpose of this study is to provide insights into the molecular, genetic, cytogenetic and cellular processes that maintain genomic integrity or promote genomic instability in cells surviving exposure to ionizing radiation. Specifically this study investigates directly whether the originating event is located intra-or extranuclearly. Chromosomal instability is studied in hamster-human hybrid cells containing human chromosome 4 using fluorescence in situ hybridisation. The unique capabilities of the microbeam allow for the irradiation of cells with alpha-particles through subcellular compartments. Individual cells were imaged and irradiated with 1, 4, 8 , or 16 alpha particles through the nuclear centroid or through the cytoplasm .Cells were maintained in culture for 20-30 cellular divisions as individual clones. Chromosomally aberrant sub-clones were found for nuclear and cytoplasmic irradiations.It is highly probable that a DNA double strand break is not the most efficient initiator of genomic instability.
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