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Regulation and significance of apoptosis in stem cells of the gastrointestinal epithelium

机译：胃肠天皮干细胞细胞凋亡的调节和意义

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Cancer of the colorectal region of the gastrointestinal tract ranks third in terms of incidence and also mortality in the UK, with about 31 000 new cases a year and about 18 000 deaths a year, with virtually the same incidence and mortality levels in males and females. Worldwide there are approximately 700 000 new cases of colorectal cancer each year. (These data come from the UK Cancer Research Campaign factsheets and relate to the years 1985 for world values, 1988 for incidence and 1993 for mortality.) The surprising fact is that cancer of the small bowel is rare, the incidence and mortality figures being marginally over 1% of the figures for colorectal cancer. There have been many attempts to provide an explanation for why colorectal cancer is relatively common, but relatively few explanations as to why small intestine cancer is rare. Some of the data to be presented here allow the hypothesis to be raised that the small intestine is protected against cancer risk, at least in part, by the high propensity of its stem cells to undergo apoptosis following DNA damage induction. The small intestine is a considerably larger organ than the large intestine, and the cells in the small intestinal crypt are proliferating nearly twice as fast as in the large bowel. The small intestine thus represents one of the most rapidly proliferating tissues of the body. In the mouse each proliferative unit, the crypt, contains about 150 rapidly dividing cells, which have a cell cycle of about half a day; as a consequence a cell enters mitosis every 5 min in each crypt. This high rate of proliferation results in about 300 cells being produced per day from each crypt and these emigrate from the crypt to the villus at a velocity of one or two cell diameters per hour. (About 10~9 cells are thus produced every 4.4 days in the mouse.) As a consequence of this cell proliferation rate and migration velocity, cells reach the tip of the villus between 2 and 3 days after birth by division in the upper regions of the crypt. Thus, most cells in the small intestinal epithelium have a functional life expectancy of only a few days. (Two to three days on the villus and perhaps another two to three days in the dividing transit compartment of the crypt.) The indications are that the cell cycle time in the large bowel is between 1 1/2 and 2 times longer than in the small intestine in both mouse and humans, and that the human cell cycle times, although poorly denned relative to the mouse, are about 3 1/2 times longer for all regions of the gastrointestinal tract. It can be estimated that in the human small intestine, with a possible cell cycle time of about 36 h and a total length of between 5 and 6 m, 10~9 cells are produced approximately every 3 h. In contrast, the mouse small intestine is about 20 cm in length. The human large intestine is about 1 1/2 m in length, compared to the 6-7 cm in the mouse (these data come from many sources and are summarized in ref. 1).
机译：胃肠道的结直肠区域癌症在英国的发病率和死亡率方面排名第三，每年约有31 000例新病例和每年约18 000人死亡，以及男性和女性的几乎相同的发病率和死亡率。全球每年大约有700 000例结直肠癌患者。 （这些数据来自英国癌症研究竞选事件，1985年为世界价值观，1988年出于死亡率和1993年的死亡率。）令人惊讶的事实是小肠的癌症是罕见的，发病率和死亡率略有超过1％的结直肠癌。有许多尝试对为什么结肠直肠癌相对普遍提供解释，但对为什么小肠癌是罕见的，少数解释。这里呈现的一些数据允许提出假设，即至少部分地部分地通过其干细胞在DNA损伤诱导后进行细胞凋亡来保护小肠免受癌症风险的影响。小肠是比大肠比大的肠道相当大的器官，并且小肠隐窝中的细胞在大肠中的快速增殖几乎是速度的两倍。因此，小肠代表了身体最快增殖的组织中的一种。在小鼠中，每个增殖单位，隐窝，含有约150个快速分裂的细胞，其细胞周期约为半天;结果，细胞在每个地穴中每5分钟进入丝分裂。这种高增殖速率导致每天从每个地下的每天产生约300个细胞，这些细胞在每小时的一个或两个细胞直径的速度下从隐窝到绒毛。 （因此在小鼠中每44天制备约10〜9个细胞。）由于这种细胞增殖率和迁移速度，细胞在出生后在上层地区出生后2至3天达到绒毛的尖端隐窝。因此，小肠上皮中的大多数细胞只有几天的功能寿命。 （别墅上两到三天，也许在Crypt的分割过境舱内又两到三天。）迹象表明，大肠杆菌中的细胞周期时间在1 1/2和2倍之间比在小鼠和人类的小肠，并且人类细胞周期时间虽然相对于小鼠较差，但对于胃肠道的所有区域约为3 1/2倍。可以估计，在人类的小肠中，大约每3小时产生约36小时的可能细胞循环时间，并且在5至6μm，10〜9个细胞之间产生。相反，小鼠小肠的长度约为20厘米。与小鼠的6-7厘米相比，人大肠的长度约为1 1/2米（这些数据来自许多来源，并且总结在REF.1）中。

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