Cytogenetic Biological Dosimetry Past, Present and Future Perspectives

Abstract Human risk assessments at low doses, low dose rates and high doses following acute exposure to ionizing radiation are of prime importance in radiation protection. These issues are of continuing importance in respect of social/economic policy relating to the industrial and medical uses of ionizing radiation, and for risk assessment among people occupationally 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. Consequently, several biological assays were developed and attempts were made to investigate formation of radiation-induced chromosome aberrations and induction of genomic instability in human lymphocytes and fibroblasts. The 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 inter- and intra-changes. Consequently, this has increased significantly the accuracy and detection limit of biological dosimetry. Newly obtained data indicate that (a) Premature chromosome condensation assay (cell fusion assay) is a unique method to be used for immediate dose assessment at low (5cGy) as well as high doses (≥3 Gy) and can accurately discriminate between whole- and partial-body exposure in case of mass casualties and accidental over-exposure to high doses of ionizing radiation, (b) Chemically induced PCC assay has the potential to be applied for biological dosimetry (by analyzing ring-chromosomes) in cases of high doses (> 4 Gy). This assay has been further validated in combination with M-FISH to assess genomic instability of primary tumors, (c) FISH-based translocation assay has the potential to assess acute as well as chronic exposure in cases of accidental as well as occupational exposure to ionizing radiation, either immediately following exposure or retrospectively by defining accumulative effects to red bone marrows. (d) There are distinct fingerprints (such as insertions and complex translocations) for high LET radiation in comparison to low LET radiation. The importance of these findings, their applications in different scenarios of accidental and occupational over-exposure to ionizing radiations, such as Japan atomic bomb survivors, Chernobyl, Istanbul, Mayak and Techa River cohorts, and future perspectives for biological dosimetry will be discussed.