英国威康桑格研究所Philip H. Jones小组在研究中取得进展。他们发现通过操控氧化还原，能够在正常食管中去除p53突变细胞。这一研究成果2019年9月发表在国际学术期刊《细胞—干细胞》上。

研究人员推测，改变对突变细胞群的选择压力可能导致它们增多或减少。研究人员通过测试低剂量电离辐射（LDIR）引起的氧化应激对转基因小鼠食道中的野生型和p53突变细胞的影响来检验该假设。研究人员发现LDIR导致野生型细胞停止增殖和分化。p53突变细胞对LDIR不敏感，并且在暴露后超越野生型细胞。值得注意的是，抗氧化剂治疗和LDIR的结合能够逆转这种作用，从而促进野生型细胞增殖和p53突变体分化，进而减少p53突变群体。因此，p53突变细胞可以通过调控氧化还原使其从正常食管中减少，这表明外部干预可用于改变衰老组织的突变情况。

据悉，随着人类年龄的增长，正常组织（如食管上皮）成为突变克隆的拼凑物。一些突变在正选择下，得到超过野生型细胞竞争优势。

附：英文原文

Title: Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation

Author: David Fernandez-Antoran, Gabriel Piedrafita, Kasumi Murai, Swee Hoe Ong, Albert Herms, Christian Frezza, Philip H. Jones

Issue&Volume: Volume 25 Issue 3

Abstract: As humans age, normal tissues, such as the esophageal epithelium, become a patchwork of mutant clones. Some mutations are under positive selection, conferring a competitive advantage over wild-type cells. We speculated that altering the selective pressure on mutant cell populations may cause them to expand or contract. We tested this hypothesis by examining the effect of oxidative stress from low-dose ionizing radiation (LDIR) on wild-type and p53 mutant cells in the transgenic mouse esophagus. We found that LDIR drives wild-type cells to stop proliferating and differentiate. p53 mutant cells are insensitive to LDIR and outcompete wild-type cells following exposure. Remarkably, combining antioxidant treatment and LDIR reverses this effect, promoting wild-type cell proliferation and p53 mutant differentiation, reducing the p53 mutant population. Thus, p53-mutant cells can be depleted from the normal esophagus by redox manipulation, showing that external interventions may be used to alter the mutational landscape of an aging tissue.

DOI: 10.1016/j.stem.2019.06.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30275-9