Potten C S, Merritt A, Hickman J, Hall P, Faranda A
CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Int J Radiat Biol. 1994 Jan;65(1):71-8. doi: 10.1080/09553009414550101.
The small intestine with its high cell proliferation, well-accepted hierarchy, high radiation susceptibility and low cancer incidence is a useful model for studying the controls of cell replacement. Apoptosis, which represents part of the overall homeostatic process, occurs spontaneously at the stem cell position in the crypts, and very small doses of radiation elevate the levels of apoptosis rapidly in this region. Other cytotoxic agents also target cells in this region including several mutagenic chemicals. Yet other drugs target cells at higher positions in the crypt indicating that all crypt cells possess the programme for apoptosis, but this is normally suppressed in many of the cells. In contrast, high doses of radiation are required to reproductively sterilize the crypts and, using clonal regeneration techniques, the number of clonogenic cells is dependent on the levels of damage induced (dose), i.e. the more injury that is induced the greater number of cells that are recruited into the clonogenic compartment. All doses of radiation trigger rapid changes in proliferation in the stem cell region which suggests that the detection of the induced cell death (even small levels, such as one apoptotic cell per crypt) is efficient and has rapid consequences. p53 may be involved in this damage recognition and apoptosis initiation. The studies to date suggest that apoptosis plays an important role in this tissue in terms of its homeostasis and its protection against carcinogenesis by removal of potentially carcinogenic damaged cells.
小肠具有高细胞增殖率、公认的细胞层级结构、高辐射敏感性和低癌症发生率，是研究细胞替代控制的有用模型。凋亡是整体稳态过程的一部分，在隐窝的干细胞位置自发发生，非常小剂量的辐射会迅速提高该区域的凋亡水平。其他细胞毒性剂也靶向该区域的细胞，包括几种诱变化学物质。还有其他药物靶向隐窝中较高位置的细胞，这表明所有隐窝细胞都具有凋亡程序，但在许多细胞中该程序通常受到抑制。相比之下，需要高剂量的辐射才能使隐窝细胞生殖性绝育，并且使用克隆再生技术，克隆形成细胞的数量取决于诱导的损伤水平（剂量），即诱导的损伤越多，被招募到克隆形成区室的细胞数量就越多。所有剂量的辐射都会引发干细胞区域增殖的快速变化，这表明对诱导的细胞死亡（即使是小水平，如每个隐窝一个凋亡细胞）的检测是有效的，并且会产生快速的后果。p53可能参与这种损伤识别和凋亡启动。迄今为止的研究表明，凋亡在该组织的稳态以及通过去除潜在致癌性受损细胞来预防癌变方面发挥着重要作用。
