EFFECT OF CAFFEINATED BEVERAGES ON COLONIC EPITHELIAL CELLS

众所周知，咖啡因在体外会影响细胞的增殖，而这 研究检测饮食中的咖啡因对结肠的影响 上皮组织。受试者的饮食控制得很好[体重 维持代谢(高脂肪、低纤维)]，摄入咖啡因 作为一个自变量。在1周基线后，对照受试者 每天喝一杯无咖啡因咖啡，咖啡因受试者 1杯无咖啡因咖啡和咖啡因(5毫克/千克体重)/天，共2周。 结肠上皮、咖啡因和Ki-ras癌基因突变的评估 使用内窥镜活检(通过柔性乙状结肠镜)、血液、 还有粪便样本。 结肠癌是人类常见的恶性肿瘤。特定的膳食成分 与其发病机制有关。咖啡因，一种常见的饮食 成分，已知可以绕过培养的细胞周期检查点 细胞和酵母中。人类组织培养细胞发育成大体结构 以及当接触咖啡因和药物时的遗传异常 造成DNA损伤(烷化剂或电离辐射)。它是 认为这些缺陷的发生是因为咖啡因破坏了生理 延缓细胞周期进程直至DNA损伤的细胞周期检查点 已经完全修好了。我们的假设是，通过类似的机制 根据体外观察，饮食中咖啡因的摄入量会影响结肠 活体内的上皮细胞。 一旦对足够的受试者群体进行了研究和实验室， 统计分析完成后，我们将能够确定 咖啡因对小鼠肾小管上皮细胞凋亡和增殖的影响 结肠粘膜。此外，咖啡因对其他 结直肠癌风险的潜在生物标记物，如表达 可以确定某些肿瘤抑制基因和癌基因。一次 这些初步分析已经完成，可以进行额外的研究 用来确定咖啡因的剂量 对结肠粘膜的影响。

It is known that caffeine can affect cell proliferation in vitro and this research examines the effect of dietary caffeine on the colonic epithelium. Subjects are given a well-controlled diet [weight maintaining, metabolic (high fat, low fiber)], with caffeine administered as an independent variable. After a 1-wk baseline, control subjects receive 1 cup of decaffeinated coffee/day and caffeine subjects receive 1 cup of decaffeinated coffee & caffeine (5 mg/kg body wt)/day for 2 wks. Assessment of colonic epithelium, caffeine, and Ki-ras oncogene mutations are performed using endoscopic biopsy (by flexible sigmoidoscopy), blood, and stool samples. Colon cancer is a common human malignancy. Specific dietary components are implicated in its pathogenesis. Caffeine, a common dietary constituent, is known to circumvent cell cycle checkpoints in cultured cells and in yeast. Human tissue culture cells develop gross structural and genetic abnormalities when exposed to caffeine along with agents that cause DNA damage (alkylating agents or ionizing radiation). It is thought that these defects occur because caffeine disrupts physiologic cell cycle checkpoints that delay cell cycle progression until DNA damage is completely repaired. Our hypothesis is that, by mechanisms similar to those observed in vitro, dietary intake of caffeine can affect colonic epithelial cells in vivo. Once a sufficient subject population is studied and laboratory and statistical analyses are completed, we will be able to determine the effects of caffeine on the extent of apoptosis and cell proliferation in the colonic mucosa. In addition, the effects of caffeine on other potential biomarkers for colorectal cancer risk, such as the expression of certain tumor suppressor genes and oncogenes, can be determined. Once these initial analyses are accomplished, additional studies can be undertaken to determine the dose of caffeine which has the greatest effect on the colon mucosa.