Frequent clones of p53-mutated keratinocytes in normal human skin
Frequent clones of p53-mutated keratinocytes in normal human skin
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DOI：
10.1073/pnas.93.24.14025
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发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Brash, DE
中科院分区：
文献类型：
--
作者：
Jonason, AS;Kunala, S;Brash, DE
癌症的多重遗传打击模型预测，正常个体应该有稳定的易患癌症但非癌性的突变细胞群体，等待进一步的遗传打击。我们报道了人类皮肤的整体标本含有p53突变的角质形成细胞的克隆斑块，这些克隆来自真皮-表皮交界处和毛囊。这些克隆，60-3000个细胞大小，以超过10个细胞/cm 2的频率存在，并且总共涉及多达4%的表皮。在暴露于阳光下的皮肤中，克隆比在遮蔽阳光的皮肤中更频繁且更大。我们得出结论，除了是致肿瘤诱变剂之外，阳光还通过有利于p53突变细胞的克隆扩增而作为肿瘤促进剂。阳光的这些联合作用导致正常个体携带大量角质形成细胞的负担，从而倾向于慢跑。
The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles, These clones, 60-3000 cells in size, are present at frequencies exceeding 10 cells per cm(2) and together involve as much as 4% of the epidermis. in sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin, We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells, These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to canter.