Chromosome aberrations determined by sFISH and G-banding in lymphocytes from workers with internal deposits of plutonium.

PURPOSE: To examine the influence of α-particle radiation exposure from internally deposited plutonium on chromosome aberration frequencies in peripheral blood lymphocytes of workers from the Sellafield nuclear facility, UK. MATERIALS AND METHODS: Chromosome aberration data from historical single colour fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding) analyses, together with more recent sFISH results, were assessed using common aberration analysis criteria and revised radiation dosimetry. The combined sFISH group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and a mean external γ-ray dose of 541 mGy. The G-banding group comprised 23 men with a mean internal red bone marrow dose of 23.0 mGy and a mean external γ-ray dose of 315 mGy. RESULTS: Observed translocation frequencies corresponded to expectations based on age and external γ-ray dose with no need to postulate a contribution from α-particle irradiation of the red bone marrow by internally deposited plutonium. Frequencies of stable cells with complex aberrations, including insertions, were similar to those in a group of controls and a group of workers with external radiation exposure only, who were studied concurrently. In a similar comparison there is some suggestion of an increase in cells with unstable complex aberrations and this may reflect recent direct exposure to circulating lymphocytes. CONCLUSIONS: Reference to in vitro dose response data for the induction of stable aberrant cells by α-particle irradiation indicates that the low red bone marrow α-particle radiation doses received by the Sellafield workers would not result in a discernible increase in translocations, thus supporting the in vivo findings. Therefore, the greater risk from occupational radiation exposure of the bone marrow resulting in viable chromosomally aberrant cells comes from, in general, much larger γ-ray exposure in comparison to α-particle exposure from plutonium.

Chromosome Aberrations Determined by FISH in Radiation Workers from the Sellafield Nuclear Facility.

Workers from the Sellafield nuclear facility (Cumbria, UK) with occupational exposures to external sources of ionizing radiation were examined for translocation frequencies in peripheral blood lymphocytes using fluorescence in situ hybridization (FISH). This is an extension of an earlier study of retired workers, and includes analyses of additional samples from the earlier collection, bringing the total to 321. Another 164 samples from both current and retired employees, including 26 repeat samples, were obtained from a new collection, thus giving a combined dataset of 459 workers. This all-male population of workers was divided into 6 dose groups comprising 97 with recorded external occupational doses <50 mGy, 118 with 50-249 mGy, 129 with 250-499 mGy, 89 with 500-749 mGy, 17 with 750-999 mGy and 9 with >1,000 mGy. Univariate analysis showed a significant association between external dose and translocation frequency (P < 0.001) with the estimate of slope ± standard error being 1.174 ± 0.164 × 10(-2) translocations per Gy. Multivariate analysis revealed that age increased the rate of translocations by 0.0229 ± 0.0052 × 10(-2) per year (P < 0.001). However, the impact of age adjustment on the radiation dose response for translocation frequencies was minor with the new estimate of slope ± standard error being 1.163 ± 0.162 × 10(-2) translocations per Gy. With the dose response for the induction of translocations by chronic in vivo low-LET radiation now well characterized, cytogenetic analysis can play an integral role in retrospective dose reconstruction of chronic exposure in epidemiological studies of exposed populations.

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

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.

Neuroferritinopathy: a new inborn error of iron metabolism.

Neuroferritinopathy is an autosomal dominant progressive movement disorder which occurs due to mutations in the ferritin light chain gene (FTL1). It presents in mid-adult life and is the only autosomal dominant disease in a group of conditions termed neurodegeneration with brain iron accumulation (NBIA). We performed brain MRI scans on 12 asymptomatic descendants of known mutation carriers. All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA.