臺灣博碩士論文加值系統

中文摘要
梅納反應，為一種常發生於食品烹煮過程中所產生的一種化學反應。在以往的研究中指出有許多的梅納反應產物具有突變性及細胞毒性。在經由我們實驗室以往的研究，選定了兩種梅納反應作為研究的材料-NO-NTA與GL1。NO-NTA在先前的研究以知在細胞實驗上有致使細胞轉形的能力。所以，我們以兩階段腫瘤促進作用的實驗模式及發炎、水腫、過氧化氫的生成及鳥胺酸脫縮脢來觀察，NO-NTA是否有促進老鼠皮膚腫瘤生成的能力。另一方面，我們也同時觀察藉由NO-NTA所引發的訊息傳遞是藉由那些分子來傳達其腫瘤促進作用的訊息。
在GL-1方面，由於先前的研究中發現，Glycine所參與的梅納反應產物是具有細胞毒性的，在此我們以細胞實驗與動物模式並行的方法，藉以觀察GL-1是否具有致使細胞轉形的能力以及是否具有腫瘤促進的能力。
在經由實驗證明後，NO-NTA確實有促進腫瘤生成的能力，且其訊息是經由活化PKC、Ras、MAPKK、MAPK、PI3 kinase及Akt等分子，在傳遞至細胞核中的分子如NF-κB、c-myc、c-jun等，而造成細胞的不正常增生。另外，以BaP作為起試劑，在以GL-1作為促進劑的細胞轉形實驗上，也發現GL-1是具有導致細胞轉形的能力且轉形後的細胞在我們植入soft agar中，也能在soft agar上生長，證明確為癌細胞。而在動物體上也透過長期的兩階段腫瘤促進模式中證實，有腫瘤的生成，進而了解GL-1同樣具有腫瘤促進的能力。

Abstract
Maillard browning is one of the most important reactions occurring during heat processing, storage and cooking of food which brings about a change in the color, flavour, functional properties and nutritional value of the food. The mutagenicity and genotoxicity of Maillard reaction products (MRPs) has recently been studied extensively. In our laboratory, we used two Maillard reaction products to be an experiment model — NO-NTA and GL1. In this study, a two-stage skin carcinogenesis protocol was used to promote CD-1 mouse skin carcinogenesis using NO-NTA. Twice weekly, for 38 weeks, topical application of NO-NTA at the concentration of 250 nmol to mice previously initiated with benzo(a)pyrene (BaP) caused 90 % of tumor incidence. However, no tumors were observed in mice treated with BaP or treated with NO-NTA alone. The NO-NTA promoted tumors observed histologically in mice shows well-differentiated sguamous cell carcinoma with invasion into the subcutaneous region.
GL1 a product of model browning system generated in the presence of sodium nitrite. A two-stage transformation protocol was used to chemically transform the mouse embryo fibroblasts C3H10T1/2 cells. To initiate transformation, the cells were treated with benzo[a]pyrene (BaP) (0.1 mg/ml), and GL1(0.01, 0.1 and 1 mg/ml) was employed subsequently to complete the transformation process. Malignant transformed foci were formed in BaP-initiated and GL1 promoted C3H10T1/2 cells after 8 wk. Cells treated with GL1 alone failed to induce transformation. However, cells initiated with BaP and promoted by cells initiated with BaP and promoted by GL1 demonstrated oncogenic properties. Cell lines transformed with GL1-transformed colonies exhibited enhanced growth rate, anchorage independence and tumorigenicity in animals relative to parent cells. These results indicate that GL1 is a new tumor promoter and may induce tumor promotion by two-stage oncogenesis. Further studies on the mechanism of action of GL1 are now in progress.
Beside, we also exam the signaling pathway of NO-NTA treated CD-1 mice skin shown that it’s signaling pathway was induced NF-κB, c-Myc and c-Jun via aactivation PKC, Ras-ERK, PI3 kinase signaling pathway.

目 錄
頁數
中文摘要……………………………………………..…………………Ⅰ
英文摘要……………………………………………….….……………Ⅱ
第一章 緒論………..………………………………………..………….1
酪胺酸亞硝酸梅納反應產物NO-NTA促進CD-1 mice 腫瘤生成作用之探討
第二章 研究目的……………………………………. …………….... 23
第三章 材 料……………………………………………………...…. 24
第四章 方 法…………………………………………………..……...27
第五章 結 果…………………………..………………………..….…44
第六章 討 論…………………………………………………………50
離胺酸亞硝酸梅納反應產物之細胞轉形及CD-1 mice 腫瘤促進作用之研究
第七章 研究目的……………………………………. ……………......52
第八章 材 料……… ……………………………………..…………. 53
第九章 方 法 …… …………………………………………………...56
第十章 結 果 …… …………………..…………………………….…73
第十一章 參考文獻……………………………………………………79
圖 表…………………………………………………………………..91

第十一章
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