臺灣博碩士論文加值系統

中文摘要
苯駢(a)芘是一種多環的芳香族碳水化合物，由有機物不完全燃燒所產生的，已被證實是一種化學致癌物。苯駢(a)芘和游離輻射線都是我們在某些機會下容易接觸到的致癌因子，所以我們想了解動物細胞在這兩種致癌因子的雙重作用之下，引發細胞轉形的能力與其分子機轉是否和它們單獨作用時有所不同。首先我們以細胞存活試驗測試苯駢(a)芘對C3H10T1/2 clone 8 細胞的細胞毒性及伽瑪射線對此細胞的敏感度，其次進行苯駢(a)芘與伽瑪射線對細胞的轉形試驗，發現伽瑪射線的劑量愈高，其對細胞的轉形作用愈強。再由以上的結果，找出細胞毒性較低的苯駢(a)芘劑量，與伽瑪射線進行雙重曝露的轉型試驗，結果發現其引發的轉形細胞群落數目比起苯駢(a)芘或伽瑪射線單獨作用時多，顯示苯駢(a)芘與伽瑪射線對細胞的雙重曝露作用具有協同的致癌轉形作用。由於細胞的癌化轉形作用可能是經由某一些訊息傳導的途徑，將致癌因子的刺激傳導到細胞核內引發基因表現上的改變所造成。c-jun/c-fos是一種快速反應基因，已知會被多種致癌因子引發活化，因此我們以北方墨點法及西方墨點法來分析苯駢(a)芘和伽瑪射線對c-jun/c-fos基因表現的誘發情形，結果如下：(1)在苯駢(a)芘對細胞的誘發實驗中看不到c-jun/c-fos基因的明顯誘發，(2)伽瑪射線對c-jun 基因只有微量的誘發，(3)在苯駢(a)芘與伽瑪射線對細胞雙重曝露後也只有c-jun基因被微量誘發。所以苯駢(a)芘與伽瑪射線可能是透過其它的訊息途徑來達到促進細胞癌化轉型的協同作用。

Abstract
Benzo[a]Pyrene (B[a]P) is a polycyclic aromatic hydrocarbon which is produced from incomplete combustion. and has been proved to be a chemical carcinogenic material. B[a]P and radiation are environmental carcinogenic factors commonly existed in our environment. In this study, we attempt to understand the transformation ability and the molecular mechanism of it after exposure to both B[a]P and radiation. First, we used survival test to examine the cytotoxicity and sensitivity of C3H10T1/2 clone 8 cells exposed to B[a]P and radiation. Second, B[a]P and radiation has been used for cell transformation test. The result demonstrates that the higher dose ofγ-ray, the stronger cellular transformation has been found. Based on this initial result, we adapted lower dose of radiation to perform double-exposure transformation test. The results indicated that double exposure of B[a]P and radiation transformed cells more efficiently than either one of them. It shows that B[a]P and radiation have synergistic effect on transformation. Transformation effect may be due to the alteration of some gene expression which is induced by extracellular stimulants (such as B[a]P and radiation) and pass through a complicate signal transduction pathway to nuclear. C-jun and c-fos are early response genes which have been shown to be induced by several carcinogenic factors. In order to examine the mechanism of B[a]P and γ-ray transformation effect, c-jun/c-fos genes expression was studies by Northern and Western blots The results are as follows : (1) B[a]P can not induce c-jun/c-fos genes expression; (2) γ-ray may slightly induce c-jun gene expression; and (3) double-exposure to B[a]P andγ-ray only causes small amount of c-jun gene induction. Therefore, through our initial studies, we conclude that the synergistic effect of B[a]P andγ-ray on the induction of cellular carcinogenic transformation may be due to other different signal transduction pathway(s).

目錄
中文摘要 ----------------------------------------------- 1
英文摘要 ----------------------------------------------- 3
緒論 ----------------------------------------------------- 5
材料與方法 ------------------------------------------- 10
結果 ----------------------------------------------------- 25
討論 ----------------------------------------------------- 33
參考文獻 ----------------------------------------------- 39
表格與圖 ----------------------------------------------- 49

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