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      Germline minisatellite mutations in workers occupationally exposed to radiation at the Sellafield nuclear facility

      , , ,
      Journal of Radiological Protection
      IOP Publishing

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          Abstract

          Germline minisatellite mutation rates were investigated in male workers occupationally exposed to radiation at the Sellafield nuclear facility. DNA samples from 160 families with 255 offspring were analysed for mutations at eight hypervariable minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32) by Southern hybridisation. No significant difference was observed between the paternal mutation rate of 5.0% (37 mutations in 736 alleles) for control fathers with a mean preconceptional testicular dose of 9 mSv and that of 5.8% (66 in 1137 alleles) for exposed fathers with a mean preconceptional testicular dose of 194 mSv. Subgrouping the exposed fathers into two dose groups with means of 111 mSv and 274 mSv revealed paternal mutation rates of 6.0% (32 mutations in 536 alleles) and 5.7% (34 mutations in 601 alleles), respectively, neither of which was significantly different in comparisons with the rate for the control fathers. Maternal mutation rates of 1.6% (12 mutations in 742 alleles) for the partners of control fathers and 1.7% (19 mutations in 1133 alleles) for partners of exposed fathers were not significantly different. This study provides evidence that paternal preconceptional occupational radiation exposure does not increase the germline minisatellite mutation rate and therefore refutes suggestions that such exposure could result in a destabilisation of the germline that can be passed on to future generations.

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          Most cited references46

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          Human minisatellite mutation rate after the Chernobyl accident.

          Germline mutation at human minisatellite loci has been studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation was found to be twice as high in the exposed families as in the control group. Mutation rate in the Mogilev families was correlated with the level of caesium-137 surface contamination, consistent with radiation induction of germline mutation.
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            Minisatellites: mutability and genome architecture.

            Minisatellites have been found in association with important features of human genome biology such as gene regulation, chromosomal fragile sites, and imprinting. Our knowledge of minisatellite biology has greatly increased in the past 10 years owing to the identification and careful analysis of human hypermutable minisatellites, experimental models in yeast, and recent in vitro studies of minisatellite recombination properties. In parallel, minisatellites have been put forward as potential biomarkers for the monitoring of genotoxic agents such as ionizing radiation. We summarize and discuss recent observations on minisatellites. In addition we take advantage of recent whole chromosome sequence data releases to provide a unifying view which may facilitate the annotation of tandem repeat sequences.
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              Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria.

              To examine whether the observed excess of childhood leukaemia and lymphoma near the Sellafield nuclear plant is associated with established risk factors or with factors related to the plant. A case-control study. West Cumbria health district. 52 Cases of leukaemia, 22 of non-Hodgkin's lymphoma, and 23 of Hodgkin's disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25 and 1001 controls matched for sex and date of birth taken from the same birth registers as the cases. Antenatal abdominal x ray examinations, viral infections, habit factors, proximity to and employment characteristics of parents at Sellafield. Expected associations with prenatal exposure to x rays were found, but little information was available on viral illnesses. Relative risks for leukaemia and non-Hodgkin's lymphoma were higher in children born near Sellafield and in children of fathers employed at the plant, particularly those with high radiation dose recordings before their child's conception. For example, the relative risks compared with area controls were 0.17 (95% confidence interval 0.05 to 0.53) for being born further than 5 km from Sellafield 2.44 (1.04 to 5.71) for children of fathers employed at Sellafield at their conception, and 6.42 (1.57 to 26.3) for children of fathers receiving a total preconceptual ionising radiation dose of 100 mSv or more. Other factors, including exposure to x rays, maternal age, employment elsewhere, eating seafood, and playing on the beach did not explain these relationships. Focusing on Seascale, where the excess incidence has predominantly been reported, showed for the four out of five cases of leukaemia and one case of non-Hodgkin's lymphoma whose fathers were employed at Sellafield and for whom dose information was obtained that the fathers of each case had higher radiation doses before their child's conception than all their matched control fathers; the father of the other Seascale case (non-Hodgkin's lymphoma) was not employed at the plant. These results seem to explain statistically the geographical association. For Hodgkin's disease neither geographical nor employment associations with Sellafield were found. The raised incidence of leukaemia, particularly, and non-Hodgkin's lymphoma among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception. The association can explain statistically the observed geographical excess. This result suggests an effect of ionising radiation on fathers that may be leukaemogenic in their offspring, though other, less likely, explanations are possible. There are important potential implications for radiobiology and for protection of radiation workers and their children.
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                Author and article information

                Journal
                Journal of Radiological Protection
                J. Radiol. Prot.
                IOP Publishing
                0952-4746
                1361-6498
                March 01 2015
                March 2015
                December 08 2014
                : 35
                : 1
                : 21-36
                Article
                10.1088/0952-4746/35/1/21
                25485533
                0f75e781-4253-439e-8b21-edf450f6fd43
                © 2014

                http://iopscience.iop.org/info/page/text-and-data-mining

                http://creativecommons.org/licenses/by/3.0/

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