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Development of animal model for cancer researches concerning diet and nutrition using rasH2 mice

使用rasH2小鼠开发有关饮食和营养的癌症研究动物模型

基本信息

批准号：
09308033
负责人：
MITSUOKA Tomotari
金额：
$ 18.56万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09308033/
关键词：
Cancer ras mice transgenic mice diet Fermentation products of lactic acid bacteria 乳酸菌発酵素産物アップルペクチン Bifidobacterium longum

项目摘要

1. To study the effects of intestinal flora on cancer development, N-methyl-nitrosourea (MNU) and N,N-diethylnitrosoamine (DEN), which induce the mutations in c-Ha-ras genes, were injected to germfree and various types of gnotobiote rasH2 mice. There were no relation between cancer development and the composition of intestinal flora.2. Although rasH2 mice were inoculated with Aαc, one of heterocyclic amines, and aflatoxin, which are strong carcinogens and ingested from the daily diet, no cancers were observed.3. Inhibitory effect of various functional foods was studied using rasH2 mice injected with 1,2-dimethylhydrazine (DMH). Apple pectin and culture condensate of Bifidobacterium longum inhibited colorectal tumors. However there were no relation between development of colorectal tumors and the intestinal environments, e.g. composition of intestinal flora, concentrations of organic acids and putrefactive products, composition of bile acids.4. Culture of Propionibacterium freudereichii, which is used as starter of cheese and is immunomodulator, did not inhibit the colorectal tumors in rasH2 mice induced by DMH. Yogurt, fermented milk by Streptococcus thermophilus and Lactobacillus burgaricus, reduced the incidence of the colorectal tumors in rasH2 mice induced by DMH. Fermented soy bean protein by single culture of Lactobacillus casei, L. fermentum, Saccharomyces cerevisiae or mixed culture of them could inhibited the colorectal tumors, but not fermented protein by Leuconostoc mesenteroides and mixed culture of this with other three strains.These results indicate that rasH2 mice are good animal model to evaluate the inhibitory effects of functional food on the colorectal tumors.

1. 为了研究肠道菌群对癌症发展的影响，将诱导c-Ha-ras基因突变的N-甲基亚硝基脲（MNU）和N，N-二乙基亚硝基胺（DEN）注射到无菌和各种类型的gnotobite rasH2小鼠体内。肿瘤的发生与肠道菌群的组成没有关系。虽然rasH2小鼠接种了杂环胺中的一种α - c和黄曲霉毒素这两种强致癌物，并从日常饮食中摄入，但未观察到癌症。用注射1,2-二甲基肼（DMH）的rasH2小鼠研究了各种功能食品的抑制作用。苹果果胶和长双歧杆菌培养凝聚物对结直肠肿瘤有抑制作用。然而，结肠直肠肿瘤的发生与肠道菌群组成、有机酸和腐败产物浓度、胆汁酸组成等肠道环境没有关系。作为奶酪发酵剂和免疫调节剂的弗氏丙酸杆菌培养对DMH诱导的rasH2小鼠结直肠肿瘤无抑制作用。由嗜热链球菌和burggaricus乳杆菌发酵的酸奶可降低DMH诱导的rasH2小鼠结肠肿瘤的发生率。单独培养干酪乳杆菌、发酵乳杆菌、酿酒酵母菌或混合培养的大豆蛋白对结直肠肿瘤有抑制作用，而肠系膜Leuconostoc及其与其他3种菌株混合培养的大豆蛋白则没有抑制作用。这些结果表明，rasH2小鼠是评价功能性食品对结直肠肿瘤抑制作用的良好动物模型。