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Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats

机译:丁酰化淀粉在基因毒素处理的大鼠中有益和剂量依赖性地影响结直肠癌标志物

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摘要

Population studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats. Five groups of 15 rats were fed AIN-93G based diets containing 0-40% HAMSB for 4 weeks then injected with (AOM) and killed 6 hours later. Large bowel total SCFA, acetate and butyrate pools and hepatic portal venous plasma total SCFA, acetate and butyrate concentrations were higher with greater HAMSB intake. Distal colonic epithelial apoptotic index and colonic mucus thickness increased, while DNA single strand breaks decreased dose-dependently with greater HAMSB intake. Colonocyte proliferation rates were unaffected by diet. These data suggest that increasing large bowel butyrate may reduce the risk of CRC in a dose dependent manner by enhancing apoptotic surveillance in the colonic epithelium for damaged cells without promoting the risk of tumorigenesis through increased cell proliferation.
机译:人口研究表明,膳食纤维摄入量的增加可能降低结肠直肠癌(CRC)的风险,可能是通过结肠细菌发酵产生丁酸来实现的。丁酰化淀粉将丁酸酯递送至人类结肠,具有降低CRC风险的潜力,但高剂量可能通过促进上皮细胞增殖而加剧风险。在这里,我们报道了日粮丁酸化高直链淀粉玉米淀粉(HAMSB)的增加对乙氧基甲烷(AOM)诱导的大鼠远端结肠DNA损伤,细胞增殖,粘液层厚度和细胞凋亡的影响。五组的15只大鼠接受含0-40%HAMSB的基于AIN-93G的饮食4周,然后注射(AOM),6小时后杀死。大肠总SCFA,乙酸盐和丁酸盐池和肝门静脉血总SCFA,乙酸盐和丁酸盐浓度随着HAMSB摄入量的增加而升高。远端结肠上皮细胞凋亡指数和结肠黏液厚度增加,而DNA单链断裂随着HAMSB摄入量的增加而呈剂量依赖性降低。饮食不影响结肠细胞的增殖速率。这些数据表明,通过提高结肠上皮细胞对受损细胞的凋亡监测,而不会通过增加细胞增殖来提高肿瘤发生的风险,增加大肠丁酸盐可以剂量依赖性的方式降低CRC的风险。

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