Cancer promotive action of secondary bile acids and preventive effect owing to feeding of diets available for their capture

大豆抗性蛋白约占微生物酶消化大豆分离蛋白所产生的不溶“高分子量”部分(HMF)的四分之一。用添加或不添加脱氧胆酸(DCA)的HMF或酪蛋白饲料喂养接受致癌治疗的F-344大鼠，每隔4周切除几个单独的结肠，但在12周内肉眼看不到肿瘤。在异常隐窝病灶(ACF)检查中，DCA饲喂酪蛋白组的ACF数量远低于其他饲料组。39周时，饲喂DCA酪蛋白组的6只大鼠(n=10)和饲喂DCA的HMF组的3只大鼠(n=9)分别移植了长轴为4.0×0.4 mm的18个肿瘤和3个长轴为2.0×0.1 mm的肿瘤，而不喂DCA的酪蛋白组仅有1个肿瘤(未喂饲DCA的HMF组为零)。也就是说，尽管ACF频繁发生，但HMF的喂养延缓了肿瘤的发展。这种作用可以通过大豆抗性蛋白捕获次级胆汁酸和执行结肠的能力来解释。同时，在回肠和空肠切除手术的幼年大鼠中，给予偶氮甲烷治疗，并添加与上述相同的添加DCA的酪蛋白饲料。39周时切除的结肠进行肿瘤病变检查。结果表明，回肠或空肠切除组在肿瘤发生率(Fisher‘s概率检验)、荷瘤大鼠等级(Mann-Whitney U检验)和肿瘤定位分布(独立性卡方检验)方面均有显著差异。此外，在缺乏Na+依赖的胆汁酸转运体的回肠切除组中，近端结肠肿瘤的意外出现频率表明，大量DCA肯定流入了结肠，从而成为促进肿瘤发生的严重危险因素。

Soybean resistant protein comprises about a quarter of the insoluble "high- molecular-weight" fraction (HMF) arising from digestion of soy protein isolate with a microbial protease. Growing F-344 rats undergoing carcinogen treatment were fed HMF- or casein-based diets supplemented with or without deoxycholic acid (DCA), from which several individual colons were excised at 4 weeks' intervals but no tumors were invisible to the naked eye within 12 weeks. On inspection of aberrant crypt foci (ACF), their count in DCA-fed casein group was far less than in other dietary groups. At 39 weeks, 6 rats of the DCA-fed casein group (n=10) and 3 rats of the DCA-fed HMF group (n=9) proved to bear 18 tumors with major axis of 4.0*0.4 mm and 3 tumors with major axis of 2.0*0.1 mm, respectively, in contrast to only a single tumor for the the DCA-unfed casein group (nil for the DCA-unfed HMF group). That is to say, HMF feeding retarded tumor development despite the frequent occurrence of ACF.This effect can be interpreted in terms of the capacity of soybean resistant protein for catching secondary bile acids and carrying out of the colon.Meanwhile, young-adult rats under resectional operations on ileum and jejunum were treated woth azoxymethane and fed the same DCA-supplemented casein diet as above-mentioned. The colons excised at 39 weeks were inspected for neoplastic lesions. As a result, it turned out that there were significant differences between both groups with ileal or jejunal resection in tumor incidence (Fisher's probability test), ranks of tumor-bearing rats (Mann-Whitney U-test) and site-oriented tumor distribution (Chi-square test for independence). In addition, the unexpected frequency of tumors at proximal colon in the ileum-resected group devoid of Na^+-dependent bile acid transporter implies that lots of DCA must have flowed into the colon and thereby served as a severe rink factor of promoting tumorigenesis.