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

次级胆汁酸的致癌作用以及通过喂养可捕获次级胆汁酸的饮食而产生的预防作用

基本信息

批准号：
09660142
负责人：
IIWAMI Kimikazu
金额：
$ 2.5万
依托单位：
Kyoto Prefectural University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

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.

大豆抗性蛋白约占由微生物蛋白酶消化大豆分离蛋白产生的不溶性“高分子量”部分（HMF）的四分之一。接受致癌物治疗的生长中的F-344大鼠被喂食以羟甲基糠醛或酪蛋白为基础的饮食，并添加或不添加脱氧胆酸（DCA），每隔4周切除几个结肠，但在12周内没有肉眼看不见的肿瘤。在异常隐窝灶（ACF）检查中，dca饲喂酪蛋白组的异常隐窝灶数量远少于其他饮食组。39周时，dca饲喂酪蛋白组6只大鼠（n=10）和dca饲喂HMF组3只大鼠（n=9）分别长出18个长轴为4.0*0.4 mm的肿瘤和3个长轴为2.0*0.1 mm的肿瘤，而未饲喂dca的酪蛋白组只有1个肿瘤（未饲喂dca的HMF组无）。也就是说，尽管ACF经常发生，但HMF喂养延缓了肿瘤的发展。这种效应可以用大豆抗性蛋白捕获次级胆汁酸并将其带出结肠的能力来解释。同时，对切除回肠和空肠的青壮年大鼠给予偶氮氧甲烷处理，并饲喂与上述相同的添加dca的酪蛋白日粮。39周切除的结肠检查肿瘤病变。结果显示，两组回肠和空肠切除在肿瘤发生率（Fisher概率检验）、荷瘤大鼠队伍（Mann-Whitney u检验）和肿瘤部位分布（独立性的卡方检验）上存在显著差异。此外，在缺乏Na^+依赖性胆汁酸转运体的回肠切除组中，近端结肠肿瘤的频率出乎意料，这意味着大量DCA必须流入结肠，从而成为促进肿瘤发生的一个严重因素。