Latta R K, Fiander H, Ross N W, Simpson C, Schneider H
Institute for Biological Sciences, National Research Council of Canada, Ottawa.
Cancer Lett. 1993 Jul 16;70(3):167-73. doi: 10.1016/0304-3835(93)90227-z.
Quantitative aspects of bile acid cytotoxicity to colon cancer cell lines were investigated because of the etiological role in colon carcinogenesis attributed to the toxic effects of bile acids on colon mucosal cells. The cytotoxicity of major colonic bile acids differed. Lithocholate was the most toxic, followed by chenodeoxycholate and deoxycholate, with cholate being non-toxic over the concentration range studied. Cytotoxicity increased with time of exposure. Values for IC50 for some of the acids were determined to be in the physiological range, as estimated from their concentrations in fecal water. The results suggest dietary factors that contribute to bile acid mucosal damage. They also identify factors of possible importance in the association of high concentrations of bile acids in fecal water with risk for colon cancer.
由于胆汁酸对结肠黏膜细胞的毒性作用在结肠癌发生的病因学中具有重要作用,因此对胆汁酸对结肠癌细胞系的细胞毒性进行了定量研究。主要结肠胆汁酸的细胞毒性各不相同。石胆酸毒性最强,其次是鹅去氧胆酸和脱氧胆酸,在所研究的浓度范围内,胆酸无毒。细胞毒性随暴露时间的增加而增加。根据粪便水中某些酸的浓度估计,其中一些酸的半数抑制浓度(IC50)值处于生理范围内。结果表明饮食因素会导致胆汁酸对黏膜的损伤。它们还确定了粪便水中高浓度胆汁酸与结肠癌风险之间关联中可能重要的因素。