Technical Report No. 1-87
Frequency of somatic cell mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors
Nakamura N, Akiyama M, Kyoizumi S, Langlois RG, Bigbee WL, Jensen RH, Bean MAEditor’s note: A publication based on this report was published in Science 236:445-8, 1987.
Summary
A recently developed assay was used to measure the frequency of somatic cell mutations in atomic bomb survivors at Hiroshima. In this assay the frequency of variant erythrocytes produced by erythroid precursor cells with gene expression-loss mutations at the polymorphic glycophorin A (GPA) locus was measured. Significant correlations between variant cell frequency (VF) and estimated A-bomb exposure dose were observed for three different variant cell phenotypes. The spontaneous and induced VFs obtained in this study agree well with measures of radiation-induced mutagenesis in other systems, strongly supporting a mutational origin for GPA-loss variant cells, and suggesting that the GPA system may provide a cumulative dosimeter of past radiation exposures. These results provide clear evidence for persistent elevations of specific locus mutations in A-bomb survivors. VFs for some donors differ dramatically from the calculated dose response, and these deviations appear to primarily result from statistical fluctuations in the number of mutations in the stem cell pool. Analysis of these statistical fluctuations provides an estimate of the number of long-lived hematopoietic stem cells in humans.
A recently developed assay was used to measure the frequency of somatic cell mutations in atomic bomb survivors at Hiroshima. In this assay the frequency of variant erythrocytes produced by erythroid precursor cells with gene expression-loss mutations at the polymorphic glycophorin A (GPA) locus was measured. Significant correlations between variant cell frequency (VF) and estimated A-bomb exposure dose were observed for three different variant cell phenotypes. The spontaneous and induced VFs obtained in this study agree well with measures of radiation-induced mutagenesis in other systems, strongly supporting a mutational origin for GPA-loss variant cells, and suggesting that the GPA system may provide a cumulative dosimeter of past radiation exposures. These results provide clear evidence for persistent elevations of specific locus mutations in A-bomb survivors. VFs for some donors differ dramatically from the calculated dose response, and these deviations appear to primarily result from statistical fluctuations in the number of mutations in the stem cell pool. Analysis of these statistical fluctuations provides an estimate of the number of long-lived hematopoietic stem cells in humans.