Abstract
亞砷酸鈉(sodium arsenite), 是一種環境致癌毒物,但是對其詳細的致癌 機制仍不清楚。 前人的研究指出亞砷酸鈉的致癌性可能與過氧化氫的產 生有關, 而且已知過氧化氫會引發細胞進行程序性細胞死亡。 因為細胞 程序性死亡與可能細胞致癌機轉有關, 本研究的主題定為： 亞砷酸鈉會 不會誘發細胞程序性死亡, 若會, 其原因為何? 在本研究的結果顯示, 當中國倉鼠卵巢細胞經在亞砷酸鈉處理 4 小時後, 再繼續培養在新鮮的 培養基 20 小時, 可觀察到細胞發生程序性死亡的現象。 但是, 在處理 亞砷酸鈉 4小時後立刻將細胞收下, 則並未觀察到程序性的細胞死亡。 所以, 由亞砷酸鈉引起的程序性的細胞死亡是一種延遲表現的細胞反應 。 外加過氧化氫酵素 (catalase), 會降低由亞砷酸鈉引起的程序性細 胞死亡的比例。 相反地,過氧化氫酵素的抑制劑 3-amino-1,2,4, triazole, 會降低過氧化氫酵素的活性, 並且會增加由亞砷酸鈉引起的程 序性的細胞死亡的比例, 及對細胞的毒性。 過氧化氫酵素缺陷的 XRS-5 細胞, 其對亞砷酸鈉比其母細胞株 CHO-K1 細胞敏感, 並且也會有較高 比例的程序性死亡的細胞。 所以, 亞砷酸鈉可能是藉由氧化活性物 (reactive oxygen species)的生成引發細胞進行程序性死亡的現象。 Arsenic, a potent human carcinogen, is toxic to mammalian cells, however, its toxic mechanism has not been clearly understood. It has been suggested that arsenic treatment produces oxidative stress. I show that CHO-K1 cells treated with sodium arsenite (SA) for 4 h followed by a 20 h incubation in fresh medium resulted in apoptosis. No apoptosis was observed immediately after a SA 4 h treatment. The results indicated that SA-induced apoptosis was a delayed response. Pretreatment of CHO- K1 cells with cycloheximide(a protein synthesis inhibitor) or actinomycin D (an RNA synthesis inhibitor) for 1 h decreased the number of SA-induced apoptosis. These results indicate that newly synthesized RNA and protein were required for the SA-induced apoptosis. It is known that H2O2 can induce apoptosis in mammalian cells, and I have found that SA treatment increased the production of H2O2. Addition of catalase to cell culture medium reduced the SA- induced apoptosis. In contrast, addition of 3- amino-1,2,4- triazole (a catalase inhibitor)increased the SA-induced apoptosis. Catalase-deficient cells, XRS-5, also produced more apoptosis comparing to the parental cells, CHO-K1, after SA treatment. Dimethyl sulfoxide, a hydroxyl radical scavenger also decreased the SA-induced apoptosis. These data suggest that SA-induced apoptosis may be mediated by the generation of reactive oxygen species.