Potten C S, Chadwick C A
Department of Epithelial Cell Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Growth Factors. 1994;10(1):63-75. doi: 10.3109/08977199409019604.
Following a dose of 8 Gy of gamma-rays delivered to the entire body of BDF1 mice, the proliferative activity in the crypts of the small intestine changes. The labelling and mitotic activity both fall precipitously, but in the lower regions of the crypt recovery from this fall begins soon after irradiation with cyclic fluctuations. Forty-five to fifty hours after irradiation, control levels are reached after which there is an overshoot. The number of clonogenic cells in the crypt shows a somewhat similar pattern of regeneration and overshoot. It has been assumed that these changes reflect the production of endogenous signals for proliferation and inhibition and these might be extracted by diffusion through the gut wall. We report here that at appropriate times after irradiation stimulatory and inhibitory extracts could be prepared. Appropriate in vivo assay techniques have been developed for testing inhibitors or stimulators making similar use of the patterns of proliferative regeneration after irradiation. Extracts prepared at either 15 h or 39 h after irradiation, i.e. during the phase of active regeneration are quite potently stimulatory on recipient animals 96 h after irradiation (i.e., following the decline from a proliferative overshoot) when injected twice 3 h apart. Extract prepared 72 h after irradiation (shortly after the overshoot peak) is strongly inhibitory when tested on unirradiated animals, or animals 90 h after irradiation, when injected four times 2 h apart. An accompanying paper shows that the stimulatory extract is powerfully active on intestinal cell lines. The in vitro approach is currently being used to characterise the stimulatory factor.
给BDF1小鼠全身照射8 Gy的γ射线后，小肠隐窝中的增殖活性会发生变化。标记活性和有丝分裂活性均急剧下降，但在隐窝的较低区域，照射后不久这种下降就开始恢复，并伴有周期性波动。照射后45至50小时达到对照水平，之后会出现超调。隐窝中的克隆形成细胞数量显示出类似的再生和超调模式。据推测，这些变化反映了内源性增殖和抑制信号的产生，并且这些信号可能通过肠壁扩散而被提取出来。我们在此报告，在照射后的适当时间可以制备刺激提取物和抑制提取物。已经开发出合适的体内测定技术来测试抑制剂或刺激剂，这些技术利用了照射后增殖再生的模式。在照射后15小时或39小时制备的提取物，即在活跃再生阶段，当每隔3小时注射两次时，对照射后96小时的受体动物（即，在增殖超调下降之后）具有相当强的刺激作用。照射后72小时（超调峰值后不久）制备的提取物，当对未照射的动物或照射后90小时的动物进行测试时，每隔2小时注射四次，具有强烈的抑制作用。一篇随附的论文表明，刺激提取物对肠细胞系具有强大的活性。目前正在使用体外方法来表征刺激因子。
