Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
Nutr Res Rev. 2001 Dec;14(2):229-56. doi: 10.1079/NRR200128.
There is now ample epidemiological evidence to show that the wide international variations in the incidence of both adenomatous polyps and colo-rectal cancer are linked to diet, but the mechanisms through which particular dietary constituents influence the onset of neoplasia are poorly understood. The crypt epithelial cells of the human gastrointestinal mucosa are amongst the most rapidly proliferating tissues in the body, and those of the colorectum are particularly vulnerable to neoplasia. Within the crypt, continuous division of basally localized stem cells gives rise to daughter cells that may divide once or twice again, before differentiating and migrating to the mucosal surface. The majority of nascent crypt epithelial cells differentiate, become senescent and are shed into the gut lumen, but a small proportion die by apoptosis soon after cell division. Various lines of evidence suggest that these pathways of programmed cell death provide a protective mechanism against induction of neoplasia by removing genetically damaged stem cells before they can divide further and give rise to precancerous lesions. There is evidence that the short-chain fatty acid butyrate and several different classes of food constituents, including some polyunsaturated fatty acids, flavonoids and glucosinolate breakdown products, can regulate the processes of cell proliferation and death in vitro, and in colorectal crypts in vivo. All three classes of food components suppress the emergence of aberrant crypt foci in animal models of carcinogenesis. The cellular mechanisms underlying these phenomena, and their possible significance for human health, are discussed.
现在有充分的流行病学证据表明，腺瘤性息肉和结直肠癌的发病率在国际范围内存在广泛差异，这与饮食有关，但特定饮食成分影响肿瘤发生的机制还知之甚少。人体胃肠道黏膜的隐窝上皮细胞是体内增殖最快的组织之一，而结直肠的隐窝上皮细胞特别容易发生肿瘤。在隐窝中，基底定位的干细胞不断分裂，产生的子细胞可能再分裂一次或两次，然后分化并迁移到黏膜表面。新生的隐窝上皮细胞大多数分化、衰老并脱落到肠腔中，但一小部分在细胞分裂后不久通过细胞凋亡而死亡。有各种证据表明，这些程序性细胞死亡途径通过在具有遗传损伤的干细胞进一步分裂并产生癌前病变之前将其去除，提供了一种针对肿瘤发生的保护机制。有证据表明，短链脂肪酸丁酸和几类不同的食物成分，包括一些多不饱和脂肪酸、类黄酮和硫代葡萄糖苷的分解产物，能够在体外和体内的结直肠隐窝中调节细胞增殖和死亡的过程。这三类食物成分都能抑制致癌动物模型中异常隐窝病灶的出现。讨论了这些现象背后的细胞机制及其对人类健康的可能意义。
