摘要：
WTK1與TK6細胞同樣是前人自WI-L2細胞中，篩選具聚落形成(colony-forming)能力的淋巴母細胞，經過相同變異誘發與篩選過程所得。過去，本實驗室發現WTK1與TK6細胞有相同的砷吸收與累積情形，然而WTK1細胞在相同濃度亞砷酸鈉(NaAsO2)及三氯化銻(SbCl3)4小時處理，更換無藥培養液培養24小時的實驗中，細胞樣本中sub-G1細胞比率較TK6細胞低。

本篇論文就WTK1與TK6細胞處理同濃度的亞砷酸鈉與三氯化銻所產生的細胞毒理反應(cytotoxicity)高低不同，對細胞因亞砷酸鈉或三氯化銻刺激所產生的NO (一氧化氮，nitric oxide)、GSH (穀胱甘 ，glutathione)、GPx(穀胱甘 過氧化酵素，glutathione peroxidase)以及catalase(過氧化氫酵素)進行檢測。WTK1細胞對亞砷酸鈉及三氯化銻的處理，不論是細胞樣本中sub-G1細胞比率的增加或細胞活力(viability)降低的實驗，均表現較TK6細胞高的耐受性。在藥物4小時處理的觀察中，WTK1與TK6細胞中有RNS/ROS (活性氮化物/活性氧化物，reactive nitrogen species/ reactive oxygen species)增加的情形；隨亞砷酸鈉或三氯化銻處理濃度增加，兩細胞中NO產生的增加情形以WTK1細胞較多，GSH含量則僅在TK6細胞中有下降的趨勢，而抗氧化酵素GPx比活性(specific activity)，也有隨藥物處理濃度增加的傾向，不過catalase酵素比活性則未呈現變動。量測亞砷酸鈉或三氯化銻4小時處理後，細胞更換無藥培養液培養情況中的catalase酵素比活性，發現catalase酵素比活性在藥物處理後出現因藥物處理濃度的高低而不同的降低情形，且TK6細胞中catalase酵素比活性在同濃度藥物處理後降低的情形較WTK1細胞顯著。然而，以NAME (N□-nitro-L-arginine methyl ester，抑制NO合成)、SNP (sodium nitroprusside，刺激細胞NO產生)、BSO (L-buthionine-[S, R]-sulfoximine，降低GSH)、MS (mercaptosuccinic acid，抑制GPx) 以及AT (aminotriazole，抑制catalase)等藥物與亞砷酸鈉或三氯化銻共同處理的結果，顯示只有NAME、SNP與BSO會影響WTK1與TK6細胞在亞砷酸鈉或三氯化銻處理後出現的細胞活力差異現象。

本論文實驗結果顯示：NO與GSH可能與WTK1和TK6細胞間的亞砷酸鈉或三氯化銻耐受性高低有關；抗氧化酵素GPx和catalase會因砷或銻處理而發生變動，但與WTK1和TK6細胞間的差異無顯著關聯。

Abstract:
WTK1 and TK6 cell lines were derived with both the same mutagenic treatment and mutation selection from different colony-forming subclones of the spleen nonclonal lymphoblastoid isolate--WI-L2. We found that there was a lower sub-G1 cell ratio in WTK1 cell than TK6 cell after incubation in fresh medium for 24 hours with the previous identical concentration 4 hours treatment of sodium arsenite (NaAsO2) or antimony chloride (SbCl3) while the same intake and accumulation of arsenite was performed.

Basing on the difference in cytotoxicity response of WTK1 and TK6 cells after sodium arsenite or antimony chloride treatment, the alternations of NO (nitric oxide), GSH (glutathione), GPx (glutathione peroxidase), and catalase induced by the treatment were examined. WTK1 cells performed a stronger resistance toward sodium arsenite and antimony chloride to TK6 cells in views of sub-G1 cell ratio raise and cell viability decrease. After the 4 hours treatment of arsenite or antimony, there were intracellular RNS/ROS (reactive nitrogen species/ reactive oxygen species) increases in both WTK1 and TK6 cells. With the treatment concentrations of sodium arsenite or antimony chloride raising, the intercellular NO levels were increased more in WTK1 cells, the intracellular GSH amounts were decreased only in TK6 cells, and the GPx specific activities of both cell lines were increased while no obvious change was seen in catalase. The catalase specific activity change of cells incubated in fresh medium after the 4 hours treatment of sodium arsenite or antimony chloride was found to be responsively decreased with different drug concentrations, and larger decrease was seen in TK6 cells in the same treatment. However, after the co-treatments of NAME (N□-nitro-L-arginine methyl ester), SNP (sodium nitroprusside), BSO (L-buthionine-[S, R]-sulfoximine), MS (mercaptosuccinic acid), and AT (aminotriazole) with sodium arsenite or antimony chloride respectively, it was found that only the co-treatments of NAME, SNP and BSO had effects on cell viability decrease.

To sum up, in this thesis, it was suggested that NO and GSH might be involved in the difference of WTK1 and TK6 cell lines toward sodium aresnite and antimony chloride treatments. Intracellular GPx and catalase were changed by the treatments, but their changes might not be involved in the difference.

中英摘要…………………………… 1

簡 介…………………………… 5

實驗方法……………………………13

結 果……………………………16

討 論……………………………22

參考資料……………………………27

圖 表……………………………41

附 錄……………………………59

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