Bile acid concentrations, cytotoxicity, and pH of fecal water from patients with colorectal adenomas
Bile acid concentrations, cytotoxicity, and pH of fecal water from patients with colorectal adenomas
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DOI：
10.1023/a:1026644418142
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发表时间：
1999-11-01
影响因子：
3.1
通讯作者：
Kleinjans, JCS
中科院分区：
文献类型：
--
作者：
de Kok, TMCM;Van Faassen, A;Kleinjans, JCS
在人类大肠肿瘤发生的多阶段模型中，遗传和环境因素都起着重要作用，然而，所涉及的环境因素的身份仍有待阐明。由于粪便胆汁酸被提议作为候选物，我们比较了来自不同发展结直肠癌风险的患者的粪便水中胆汁酸的浓度。此外，还测定了粪便水的pH值及其对HT-29结肠细胞的细胞毒性。高风险组由被诊断患有一个或多个直径大于1 cm且含有中度或重度异型增生的（管状）绒毛状结直肠腺瘤的个体组成（N = 20）。患有小于1 cm且仅显示轻微异型增生的结直肠腺瘤的受试者被分配到中等风险组（N = 19）。对照组为结肠镜检查正常者（N = 25），三组间粪水胆汁酸浓度无显著性差异。然而，46%的观察到的细胞毒性在包括pH值和脱氧胆酸、胆酸和熊去氧胆酸浓度的回归模型中得到解释。与对照组相比，高风险组粪便水的pH值显著降低，表明相对较高的粪便pH值对结直肠腺瘤的发展具有保护作用。虽然细胞毒性导致的过度增殖被认为是结肠肿瘤形成的原因，但在本研究中，未发现粪便水中胆汁酸的pH依赖性细胞毒性与腺瘤形成相关。
In the multistage model of human colorectal tumorigenesis, both genetic and environmental factors play an important role, The identity of the environmental factors involved, however, still remains to be elucidated. As fecal bile acids are proposed as candidates, we compared the concentration of bile acids in fecal water from patients at different risk of developing colorectal cancer. In addition, pH of fecal water as well as its cytotoxicity to HT-29 colonic cells was determined. The high-risk group consisted of individuals diagnosed with one or more (tubulo)villous colorectal adenomas larger than 1 cm in diameter and containing moderate or severe dysplasia (N = 20), Subjects with colorectal adenomas smaller than 1 cm and showing only minor dysplasia were assigned to the medium risk group (N = 19), The control group consisted of persons with normal findings by colonoscopy (N = 25), The results show no significant differences in fecal water bile acid concentrations between the three groups. However,46% of the observed cytotoxicity is explained in a regression model that includes pH and the concentrations of deoxycholic acid, cholic acid, and ursodecaxycholic acid. The pH of fecal water is found to be significantly lower in the high risk group as compared to the controls, suggesting that a relatively high fecal pH has a protective effect on the development of colorectal adenomas. Although hyperproliferation as a result of cytotoxicity has been suggested to contribute to tumor formation in the colon, the pH-dependent cytotoxicity of bile acids in fecal water was not found to be associated with adenoma formation in the present study.