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原子弹爆炸幸存者中糖蛋白A位点体细胞突变增加的证据。

Evidence for increased somatic cell mutations at the glycophorin A locus in atomic bomb survivors.

作者信息

Langlois R G, Bigbee W L, Kyoizumi S, Nakamura N, Bean M A, Akiyama M, Jensen R H

出版信息

Science. 1987 Apr 24;236(4800):445-8. doi: 10.1126/science.3563520.

DOI:10.1126/science.3563520
PMID:3563520
Abstract

A recently developed assay for somatic cell mutations was used to study survivors of the atomic bomb at Hiroshima. This assay measures the frequency of variant erythrocytes produced by erythroid precursor cells with mutations that result in a loss of gene expression at the polymorphic glycophorin A (GPA) locus. Significant linear relations between variant frequency (VF) and radiation exposure were observed for three different variant cell phenotypes. The spontaneous and induced VFs agree with previous measurements of radiation-induced mutagenesis in other systems; this evidence supports a mutational origin for variant cells characterized by a loss of GPA expression and suggests that the GPA assay system may provide a cumulative dosimeter of past radiation exposures. VFs for some survivors differ dramatically from the calculated dose response, and these deviations appear to result primarily from statistical fluctuations in the number of mutations in the stem-cell pool. These fluctuations allow one to estimate the number of long-lived hemopoietic stem cells in humans.

摘要

一种最近开发的体细胞突变检测方法被用于研究广岛原子弹爆炸的幸存者。该检测方法测量由红系前体细胞产生的变异红细胞的频率,这些细胞发生的突变导致多态性血型糖蛋白A(GPA)位点的基因表达缺失。对于三种不同的变异细胞表型,观察到变异频率(VF)与辐射暴露之间存在显著的线性关系。自发和诱导的VF与之前在其他系统中辐射诱导诱变的测量结果一致;这一证据支持了以GPA表达缺失为特征的变异细胞的突变起源,并表明GPA检测系统可能提供过去辐射暴露的累积剂量计。一些幸存者的VF与计算出的剂量反应有很大差异,这些偏差似乎主要是由于干细胞库中突变数量的统计波动造成的。这些波动使人们能够估计人类中长寿造血干细胞的数量。

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