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

1.为探讨肠道植物群对肿瘤发生的影响，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）分别注射给无菌和不同类型的gnotobiote rasH 2小鼠。肠道菌群组成与肿瘤的发生无关.尽管rasH 2小鼠接种了Aαc（一种杂环胺）和黄曲霉毒素（从日常饮食中摄入的强致癌物），但未发生癌症.使用注射1，2-二甲基肼（DMH）的rasH 2小鼠研究了各种功能性食品的抑制作用。苹果果胶和长双歧杆菌培养物浓缩物抑制结直肠肿瘤。而大肠肿瘤的发生与肠道环境如肠道植物群组成、有机酸和腐败产物浓度、胆汁酸组成等无明显关系.作为干酪发酵剂和免疫调节剂的费氏丙酸杆菌培养物对DMH诱导的rasH 2小鼠结直肠肿瘤无抑制作用。酸奶、嗜热链球菌和保加利亚乳杆菌发酵乳可降低DMH诱导的rasH 2小鼠结直肠肿瘤的发病率。干酪乳杆菌、乳酸菌、乳酸菌单一培养物发酵大豆蛋白。结果表明，rasH 2小鼠是评价功能性食品对大肠肿瘤抑制作用的良好动物模型。

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.