Campbell F, Williams G T, Appleton M A, Dixon M F, Harris M, Williams E D
Department of Pathology, University of Wales, College of Medicine, Cardiff.
Gut. 1996 Oct;39(4):569-73. doi: 10.1136/gut.39.4.569.
Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics.
To study the clonal stabilisation time in the human colorectum.
Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy.
Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation.
Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.
结肠直肠隐窝是克隆单位，其中干细胞中标记基因的体细胞突变会导致隐窝受限的表型转换，最初涉及部分隐窝，随后涉及整个隐窝。对小鼠的研究表明，绝大多数突变隐窝完全转换所需的时间，即克隆稳定时间，在结肠中为四周，在回肠中为21周。组织和物种之间克隆稳定时间的差异被认为反映了干细胞组织和隐窝动力学的差异。
研究人类结肠直肠的克隆稳定时间。
对于O - 乙酰转移酶基因活性杂合的受试者，干细胞突变可导致唾液粘蛋白O - 乙酰化的隐窝受限缺失。采用mPAS组织化学法对21例接受放疗后长达34年进行结肠切除术的信息丰富病例中部分或完全受突变表型影响的隐窝进行可视化和定量分析。
放疗后不一致隐窝频率显著增加，且多年来一直显著升高。显示部分受累的不一致隐窝比例最初较高，但在照射后约12个月降至正常水平。
完全受突变表型影响的隐窝是稳定且持久的，而部分受累的隐窝是短暂的。人类结肠中的克隆稳定时间约为一年，而小鼠为四周。最可能的原因是隐窝干细胞龛中干细胞数量的差异，尽管干细胞周期时间和隐窝裂变的差异也可能起作用。这些发现与结肠直肠基因治疗和干细胞系统中的致癌作用相关。
