Abstract
f.darroudi@lumc.nl 1. Abstract: The importance of detecting risks at the low doses (<5cGy) and low dose rates in radiation protection is well recognised. Similar issues surround the acquisition of knowledge on common genetic factors that might determine inter-individual differences in low dose cancer risk. These aspects are of continuing importance in respect of social/economic policy relating to the industrial and medical uses of ionising radiation, and for risk assessment among people occupationally are being exposed to low and/or high LET radiation, such as astronauts, pilots, stewardess and nuclear power plant workers, as well as victims of radiation accidents. In order to emphasis on the acquisition of fundamental knowledge and the development of low dose as well as high dose risk models for low LET radiation (i.e. gamma-rays and X-rays) and high LET radiation (i.e. heavy ions, alpha-particles, neutrons), several biological assays were developed and attempts were made to investigate formation of radiation induced chromosome aberrations and induction of genomic instability in human following acute and/or chronic exposure. Newly obtained data indicate that (a) Premature chromosome condensation assay is a unique method to be used for immediate dose assessment at low does (5≥Gy) as well as high doses (≥3 Gy), and can accurately discriminate between wholeand partial-body exposure. Therefore, this is the method of choice for biodosimetry in cases of mass casualties and accidental over-exposure to high doses of ionising radiation (b) Fluorescence in situ hybridization (FISH) technique using chromosome, chromosome-arm, chromosome region, centromere and telomere specific DNA libraries has improved the resolution of detecting all classes of radiation induced chromosomal interand intra-changes. Consequently, has increased significantly the accuracy and detection limit of biological dosimetry. FISH-based translocation assay has the potential to assess biodosimetry in cases of accidental as well as occupational exposures to ionising radiation, either immediately following exposure, and in particular, retrospectively by defining accumulative effects to red bone marrows. (c) Further modification of FISH assay by either combining chromosome, centromeres and telomeres specific probes or the M-FISH assay revealed distinct finger-prints, such as insertions and complex translocations for high LET radiation in comparison to low LET radiation. KeywordsIonising radiation, Biological dosimetry, Chromosomal aberrations, PCC, FISH-based translocation, I. The importance of dose assessment in human: Considering the notion that chromosomal instability is the hallmark of cancer, it is essential to develop and validate different biological assays for dose-assessment in cases of occupational and accidental over-exposure to ionising radiation of different qualities. High doses of ionizing radiation clearly produce deleterious consequences in human, including, but not exclusively, cancer induction. Therefore, it is essential to estimate chromosomal
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