Radiation exposure leads to a risk for long-term deterministic and stochastic late effects. Two individuals exposed to protracted photon radiation in the radiological accident at the Lilo Military site in Georgia in 1997 received follow-up treatment and resection of several chronic radiation ulcers in the Bundeswehr Hospital Ulm, Germany, in 2003. Multi-parameter analysis revealed that spermatogenetic arrest and serum hormone levels in both patients had recovered compared to the status in 1997. However, we observed a persistence of altered T-cell ratios, increased ICAM1 and beta1-integrin expression, and aberrant bone marrow cells and lymphocytes with significantly increased translocations 6 years after the accident. This investigation thus identified altered end points still detectable years after the accident that suggest persistent genomic damage as well as epigenetic effects in these individuals, which may be associated with an elevated risk for the development of further late effects. Our observations further suggest the development of a chronic radiation syndrome and indicate follow-up parameters in radiation victims.
"It has been known that T-lymphocytes mature in thymus which starts degrading soon after birth (Kusunoki et al. 1998). Decreased numbers of CD4? lymphocytes were also observed among Hiroshima and Nagasaki A-bomb survivors 42–46 years after acute exposure (Kusunoki et al. 1998, 1999), in residents of Techa riverside villages 53–56 years after exposure onset (Ovcharova 2006; Akleyev 2007); relation of CD4? lymphocytes to dose was revealed both in this study and the Japanese one (Kusunoki et al. 1998) and in gamma radiation-exposed individuals of the Lilo accident (Scherthan et al. 2007). Relative and absolute concentration of CD8? subset of T-lymphocytes was altered neither in this study nor in Japanese cohort (Kusunoki et al. 1998). "
"It has been known, that T-lymphocytes differentiate in thymus which starts degrading soon after birth (Kusunoki et al. 1998). Decreased numbers of CD4+ lymphocytes was also observed among Hiroshima and Nagasaki A-bomb survivors 42-46 years after acute exposure (Kusunoki et al. 1998, 1999), in residents of Techa riverside villages 53-56 years after exposure onset (Ovcharova et al. 2006, Akleyev et al. 2007); relation of CD4+ lymphocytes to dose was revealed both in this study and the Japanese one (Kusunoki et al., 1998) and in gamma radiation-exposed individuals of the Lilo accident (Scherthan et al. 2007). Relative and absolute concentration of СD8+ subset of T-lymphocytes was altered neither in this study nor in Japanese cohort (Kusunoki et al., 1998). "
[Show abstract][Hide abstract] ABSTRACT: This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic occupational IR exposure of workers induced a depletion of immune cells in peripheral blood of the individuals involved.
"Slides were stored at −20 • C until use. Three-colour chromosome painting (FISH) with a combination of chromosome #1, #4 and #12 paint probes (MetaSystems, Altlussheim, Germany) was done as published  . Briefly: The hybridization mix was heated to 72 • C for 5 min and then incubated at 37 • C for 10 min prior to applying the mixture to the denatured chromosomes. "
[Show abstract][Hide abstract] ABSTRACT: The exposure of tumour cells to high doses of ionizing radiation can induce endopolyploidization as an escape route from cell death. This strategy generally results in mitotic catastrophe during the first few days after irradiation. However, some cells escape mitotic catastrophe, polyploidize and attempt to undergo genome reduction and de-polyploidization in order to create new, viable para-diploid tumour cell sub-clones. In search for the consequences of ionizing radiation induced endopolyploidization, genome and chromosome architecture in nuclei of polyploid tumour cells, and sub-nuclei after division of bi- or multi-nucleated cells were investigated during 7 days following irradiation. Polyploidization was induced in p53-function deficient HeLa cells by exposure to 10Gy of X-irradiation. Chromosome territories #1, #4, #12 and centromeres of chromosomes #6, #10, #X were labelled by FISH and analysed for chromosome numbers, volumes and spatial distribution during 7 days post irradiation. The numbers of interphase chromosome territories or centromeres, respectively, the positions of the most peripherally and centrally located chromosome territories, and the territory volumes were compared to non-irradiated controls over this time course. Nuclei with three copies of several chromosomes (#1, #6, #10, #12, #X) were found in the irradiated as well as non-irradiated specimens. From day 2 to day 5 post irradiation, chromosome territories (#1, #4, #12) shifted towards the nuclear periphery and their volumes increased 16- to 25-fold. Consequently, chromosome territories returned towards the nuclear centre during day 6 and 7 post irradiation. In comparison to non-irradiated cells (∼500μm(3)), the nuclear volume of irradiated cells was increased eightfold (to ∼4,000μm(3)) at day 7 post irradiation. Additionally, smaller cell nuclei with an average volume of about ∼255μm(3) were detected on day 7. The data suggest a radiation-induced generation of large intra-nuclear chromosome territories and their repositioning prior to genome reduction.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 05/2013; 756(1-2). DOI:10.1016/j.mrgentox.2013.05.004 · 3.68 Impact Factor
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