Flinders Centre for Cancer Prevention and Control, Flinders University of South Australia, Bedford Park.
Cancer Prev Res (Phila). 2011 Nov;4(11):1920-8. doi: 10.1158/1940-6207.CAPR-11-0176. Epub 2011 Sep 1.
Population studies have shown that high red meat intake may increase colorectal cancer risk. Our aim was to examine the effect of different amounts and sources of dietary protein on induction of the promutagenic adduct O(6)-methyl-2-deoxyguanosine (O(6)MeG) in colonocytes, to relate these to markers of large bowel protein fermentation and ascertain whether increasing colonic carbohydrate fermentation modified these effects. Mice (n = 72) were fed 15% or 30% protein as casein or red meat or 30% protein with 10% high amylose maize starch as the source of resistant starch. Genetic damage in distal colonocytes was detected by immunohistochemical staining for O(6)MeG and apoptosis. Feces were collected for measurement of pH, ammonia, phenols, p-cresol, and short-chain fatty acids (SCFA). O(6)MeG and fecal p-cresol concentrations were significantly higher with red meat than with casein (P < 0.018), with adducts accumulating in cells at the crypt apex. DNA adducts (P < 0.01) and apoptosis (P < 0.001) were lower and protein fermentation products (fecal ammonia, P < 0.05; phenol, P < 0.0001) higher in mice fed resistant starch. Fecal SCFA levels were also higher in mice fed resistant starch (P < 0.0001). This is the first demonstration that high protein diets increase promutagenic adducts (O(6)MeG) in the colon and dietary protein type seems to be the critical factor. The delivery of fermentable carbohydrate to the colon (as resistant starch) seems to switch from fermentation of protein to that of carbohydrate and a reduction in adduct formation, supporting previous observations that dietary resistant starch opposes the mutagenic effects of dietary red meat.
人群研究表明，大量摄入红肉可能会增加结直肠癌的风险。我们的目的是研究不同数量和来源的膳食蛋白质对结肠细胞中促突变前体物 O(6)-甲基-2-脱氧鸟苷（O(6)MeG）的诱导作用，将这些与大肠蛋白质发酵标志物相关联，并确定增加结肠碳水化合物发酵是否会改变这些作用。将 15%或 30%的蛋白质作为酪蛋白或红肉或 30%的蛋白质与 10%高直链淀粉玉米淀粉作为抗性淀粉的来源喂养给 72 只小鼠。通过免疫组织化学染色检测 O(6)MeG 和细胞凋亡来检测远端结肠细胞的遗传损伤。收集粪便用于测量 pH 值、氨、酚、对甲酚和短链脂肪酸（SCFA）。与酪蛋白相比，红肉组的 O(6)MeG 和粪便对甲酚浓度明显更高（P < 0.018），并且在隐窝顶端的细胞中积累了前体物。DNA 加合物（P < 0.01）和细胞凋亡（P < 0.001）较低，而抗性淀粉喂养的小鼠的蛋白质发酵产物（粪便氨，P < 0.05；酚，P < 0.0001）较高。抗性淀粉喂养的小鼠的粪便 SCFA 水平也较高（P < 0.0001）。这是首次证明高蛋白饮食会增加结肠中的促突变前体物（O(6)MeG），并且似乎是蛋白质类型是关键因素。将可发酵碳水化合物输送到结肠（如抗性淀粉）似乎从蛋白质发酵切换到碳水化合物发酵，并且加合物形成减少，这支持了之前的观察结果，即膳食抗性淀粉可以抵抗膳食红肉的致突变作用。
