正常人皮肤中p53突变角质形成细胞的频繁克隆。
Frequent clones of p53-mutated keratinocytes in normal human skin.
作者信息
Jonason A S, Kunala S, Price G J, Restifo R J, Spinelli H M, Persing J A, Leffell D J, Tarone R E, Brash D E
机构信息
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14025-9. doi: 10.1073/pnas.93.24.14025.
Abstract
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 40 cells per cm2 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 cancer.
摘要
癌症的多重基因打击模型预测，正常个体应具有易于患癌但未癌变的突变细胞稳定群体，等待进一步的基因打击。我们报告称，人类皮肤的整装标本中含有p53突变角质形成细胞的克隆斑块，这些斑块起源于真皮-表皮交界处和毛囊。这些克隆体大小为60 - 3000个细胞，出现频率超过每平方厘米40个细胞，总共累及高达4%的表皮。在阳光暴露的皮肤中，克隆体比在防晒皮肤中更频繁且更大。我们得出结论，除了作为致瘤诱变剂外，阳光还通过促进p53突变细胞的克隆扩增而充当肿瘤促进剂。阳光的这些联合作用导致正常个体携带大量易患癌症的角质形成细胞负担。
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