Somatic Cell Mutations at the Glycophorin A Locus in Erythrocytes of Radiation Workers from the Sellafield Nuclear Facility

Abstract

The glycophorin A (GPA) somatic mutation assay for N0 and NN mutant erythrocytes was performed on 245 current and 48 retired workers who had been occupationally exposed to radiation at the British Nuclear Fuels plc facility at Sellafield. A positive association with increasing age was found for current workers for both N0 and NN frequencies of 0.14 +/- 0.05 x 10(-6) (P = 0.012) and 0.25 +/- 0.07 x 10(-6) (P = 0.0003) per year, respectively. No association with age was found for the retired workers. In a comparison of ever-smokers with never-smokers, no difference was observed for N0 frequencies for current workers, but a significantly higher frequency was found for ever-smokers in the retired group (P = 0.001). NN mutant frequencies were slightly higher in ever-smokers than in never-smokers for both current and retired workers, but in neither case was the increase significant. In age-adjusted analyses for N0 mutant frequencies, a slight positive radiation dose response was found for current workers (1.6 +/- 3.8 x 10(-6) per Sv), for retired workers (2.9 +/- 2.5 x 10(-6) per Sv), and in the combined analysis (2.6 +/- 2.2 x 10(-6) per Sv), but in no case did this reach significance. Similar analyses for NN mutant frequencies revealed a positive dose response for current workers (4.7 +/- 4.6 x 10(-6) per Sv) and a negative response for retired workers (-2.4 +/- 3.6 x 10(-6) per Sv) that was maintained in the combined analysis (-1.4 +/- 2.8 x 10(-6) per Sv), but none of these slopes was significantly different from zero. The results suggest that the GPA mutation assay is insufficiently sensitive to be used as a biological marker of low-dose chronic exposure and provide further evidence that, in contrast to high acute radiation exposure, protracted exposure is much less effective at inducing somatic mutations in vivo.

ICRP Publication 131: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection

“…The doubling dose for GPA mutations has been estimated to be approximately 1.2 Sv, with a threshold dose of approximately 0.24 Sv (Kyoizumi et al., 1996). A sizeable threshold dose for these GPA-related mutations is most likely responsible for largely negative findings of a number of investigators who used the GPA assay to monitor mutations within erythrocytes of individuals having a prior history of very low radiation exposures (Tawn et al., 2003). (A54) The timing and expression of radiation-induced mutations within HPCs have been investigated (Kadhim et al., 1992, 1994; Wang et al., 1996; Watson et al., 1996, 2001; Kadhim and Wright, 1998; MacDonald et al., 2001; McIlrath et al., 2003).…”

“…The doubling dose for GPA mutations has been estimated to be approximately 1.2 Sv, with a threshold dose of approximately 0.24 Sv (Kyoizumi et al., 1996). A sizeable threshold dose for these GPA-related mutations is most likely responsible for largely negative findings of a number of investigators who used the GPA assay to monitor mutations within erythrocytes of individuals having a prior history of very low radiation exposures (Tawn et al., 2003).…”

Technology Assessment and Roadmap for the Emergency Radiation Dose Assessment Program

“…Other approaches have been explored as well including the use of somatic null mutations at the glycophorin A locus on the surface of blood erythrocytes, micronucleus assay, and measurement of premature chromosome condensation, PCC and all have been found to be reliable indicators of exposure over a broad dose range (0.25 to 8 Gy) in the laboratory with high doses of ionizing radiation but with poor dosimetric discrimination at lower doses (Bigbee et al, 1997;Gray and Pinkel., 1994;Jones et al, 2001;Brown et al, 1997;Tawn et al, 2003;Bedford and Dewey, 2002;Durante 1996;Kanda 1999). Variations of the PCC assay (Prasanna, 2000) may provide dose estimates in less than 24 hours for relatively high doses of ionizing radiation, but still require validation.…”