2009-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/710010摘要：結腸直腸癌為國人之主要癌症死因，大約有70%的結腸直腸癌與飲食有關。乳酸菌長久以來即被應用於各種發酵食品的製造，除可提供製品特殊的風味、質地、保存食品外，更有許多研究指出乳酸菌具有維持人體腸道內正常微生物菌相、活化免疫系統、抗氧化性、降低血液中膽固醇含量、抗腫瘤及抗致突變性等諸多生理功能。許多的研究顯示益生菌菌體和發酵產品對於致突變劑和致突變原具有抗突變和抗腫瘤活性，其抗致突變機制包括去致突變性、生物抗致突變性與blocking effect。 體外研究指出益生菌具有抗結腸癌的保護效果，但其結果不能臆測益生菌的作用機制。此外，體內試驗由於所使用的益生菌種和菌株不同，在一些文獻的再現性不高。因此使用明確的益生菌種，從體外到體內模式做有系統且完整，探討益生菌對人類結腸癌發展的影響機制有其必要。 本研究以過去本究室選取之具有較佳耐酸性pH與膽汁及抗4NQO、B[a]P、t-BOOH 或 H2O2 之抗致突變性的益生菌Bifidobacterium infantis BCRC14602與B. lactis Bb-12, Lactobacillus casei 01, L. acidophilus, L. lactis 等五株益生菌為材料。擬以三年為期，首先評估益生菌對致癌劑azoxymethane或dimethylhydrazine的基因毒性及人類結腸癌細胞HT-29增生的影響。其次，探討益生菌的抗突變性機制。最後，經由動物體內結腸癌試驗模式去研究益生菌對於大鼠結腸黏膜的癌化、腸內菌相、氧化傷害及基因表現圖譜的影響。以期闡明益生菌抗致突變劑的特性以及其抗致突變機制與抑制結腸癌細胞生長之相關特性。 <br> Abstract: Colorectal cancer is a major cause of death in Taiwan. Approximately 70% of colorectal cancer is related to diets. Probiotics are used to make many kinds of fermented foods. They not only provide unique flavor and texture, but also balance intestinal microflora, stimulate immune system, antioxidation, anticarcinogenesis and antimutagenicity. There are interests in the potential protective role of probiotics against colorectal cancer. Many studies showed that probiotics, both cells compositions and fermented products have antimutagenic and antitumor activity against mutagens and promutagens. Mechanisms of antimutagenicity are classified as desmutagenicity, bioantimutagenicity and blocking effects. Most in vitro studies provided some evidence for a protective role of probiotics against colon cancer. The results of these in vitro studies, however, could not explain the mechanisms of action. Furthermore, the in vivo studies used different kinds of probiotic species and strains, which limit the reproducibility of several observations. Future studies will be needed, both in vitro and in vivo, to elucidate the mechanisms by which probiotics may affect on colon cancer development. Several probiotics, which has been studied in our laboratory for their acid-resistance, bile salt tolerance, and antimutagenicity against 4NQO, B[a]P, t-BOOH, and H2O2, are use in this 3 years’ project. Firstly, to study the effects of probiotics on the genotoxicity of azoxymethane and dimethylhydrazine, and the proliferation of human colon cancer cell HT-29. Second, antimutagenic mechanisms of probiotics were investigated. Finally, via in vivo animal colon cancer model studies, to determine the probiotics effects on the carcinogenesis, intestinal microflora, oxidative damage and gene expression profile of colonic mucosa in rats. Results of this study will illustrate the relationship between the functionality of probiotics to their antimutagenicity and antitumor properties, which will be found valuable for academic research.益生菌結腸癌氧化傷害腸道菌相基因表現probioticcolon canceroxidative damagegut microfloragene expression