DEMONSTRATION OF SOMATIC MUTATION AND COLONIC CRYPT CLONALITY BY X-LINKED ENZYME-HISTOCHEMISTRY
DEMONSTRATION OF SOMATIC MUTATION AND COLONIC CRYPT CLONALITY BY X-LINKED ENZYME-HISTOCHEMISTRY
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DOI：
10.1038/333461a0
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发表时间：
1988-06-02
期刊：
影响因子：
64.8
通讯作者：
WILLIAMS, ED
中科院分区：
文献类型：
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作者：
GRIFFITHS, DFR;DAVIES, SJ;WILLIAMS, ED
杂合女性 1 中 X 染色体失活导致的细胞嵌合现象可以通过组织化学显示 2-4；使用这种方法，我们已经证明了与年龄相关的基因再激活5和肿瘤克隆性6。我们现在发现，在葡萄糖-6-磷酸脱氢酶（G6PD）活性表达降低的杂合雌性小鼠中，结肠上皮细胞表达正常或低酶活性，并形成由多个具有一致表型的隐窝组成的斑块。我们还发现，致癌物治疗可在正常小鼠中诱导低酶结肠上皮细胞表型，这些细胞再次以斑块形式出现，但仅限于分散的单个隐窝，其频率与治疗有关。经致癌物处理的正常小鼠中的一小部分结肠肿瘤也具有低酶表型。我们得出的结论是，我们已经观察到散发性致癌物诱导隐窝干细胞 G6PD 基因体细胞突变的影响，并且单个干细胞维持着每个结肠隐窝。普遍存在的“管家”酶的这种可诱导的缺陷活性提供了具有广泛潜在应用的体细胞克隆标记系统。
Cellular mosaicism resulting from X-chromosome inactivation in heterozygous females1can be shown histochemically2–4; using this approach we have demonstrated age-related gene reactivation5and tumour clonality6. We now show in female mice heterozygous for reduced expression of glucose-6-phosphate dehydrogenase (G6PD) activity that colonic epithelial cells express either normal or low enzyme activity, and form patches composed of multiple crypts of uniform phenotype. We also show that a low-enzyme colonic epithelial cell phenotype can be induced in normal mice by car-cinogen treatment, these cells again occur in patches, but are restricted to scattered single crypts, the frequency of which is related to treatment. A small proportion of colonic tumours in carcinogen treated normal mice are also of low-enzyme phenotype. We conclude that we have visualized the effects of a sporadic carcinogen induced somatic mutation in theG6PDgene of crypt stem cells and that a single stem cell maintains each colonic crypt. This inducible defective activity of a ubiquitous 'housekeeping' enzyme provides a somatic clonal marker system of wide potential application.