Abstract
砷化物是廣泛分佈的天然毒性物質，生體外研究指出，砷化物能 發染色體異常(chromosome aberrations)、姐妹染色分體互換(sisterhromatid exchanges)，肺臟細胞專一性的核酸鏈斷裂和核酸與蛋白質ㄔ膨`的結合體 (DNA-protein crosslinking)，人體長期砷暴露會增加皮均B肺、膀胱或肝臟癌症的發生，但砷誘發癌症的分子機制仍不明A，雖然自由基涉及的假說曾被提出。因為X-射線敏感之中國倉鼠卵_細胞(xrs-5)，對數種自由基產生劑，包括過氧化氫，均呈現敏感，畯怳D利用此細胞株來測試三價砷之遺傳毒性是否經由反應性含氧物□reactive oxygenspecies)之產生來媒介。實驗結果顯示：麩胱甘太轉噱簿□glutathioneS-transferase)、麩胱甘太還原酵素 (glutathioneeductase)及過氧化物歧化酵素 superoxide dismutase)，在xrs-5與親本茩M株CHO-K1之間並無明顯差別。然而，過氧化氫分解酵素catalase) 和麩胱甘太過氧化酵素(glutathionexrs-5細M比CHO-K1細胞分別低六及七倍；在細胞外添加過氧化氫酵素及麩皏怳蚢L氧化酵素，均能降低三價砷在xrs-5細胞所誘發之微小核球micronucleus)；CHO-K1細胞前處理一種麩胱甘太過氧化酵素抑制砥A氫硫基丁二酸鹽(mercaptosuccinate)，會增強三價砷和過氧化氫所今o的微小核球；若同時處理氫硫基丁二酸鹽和一過氧化氫酵素抑制砥A3-氨基-1,2,4,-三氮二烯五圜(3-aminotriazole)，更是協力增加三價~在CHO-K1細胞所誘發之微小核球。此外，一種麩胱甘太過氧化酵嶼〝坅P進劑，亞硒酸鈉，則明顯地降低三價砷和過氧化氫所誘發的L小核球。這些數據都表示：氧化性核酸傷害應涉及三價砷在中國倉咩Z巢細胞微小核球之誘發。在所有可能性的致癌劑中，反應性含氧姿堻Q認為涉及於不同型態的人類癌症之發生，過氧化氫會誘發細胞{序性凋亡 (apoptosis)。此等事實暗示三價砷亦可能介由氧化性傷害蚖今o細胞進行程序性凋亡。細胞逃脫程序性凋亡之調控可能會進磍糷?C有關砷如何引起細胞死亡與細胞如何逃脫正常死亡路線的壅恁A對了解砷的致癌機轉可能會有所幫助，因此，我們乃研究亞砷譯u在CHO-K1細胞所誘發細胞死亡的特性。在磷酸與檸檬酸緩衝溶Arsenic compounds are widely distributed natural toxicants.nvitro studies indicate that arsenic compounds caninducehromosome aberrations, sister-chromatid exchanges, andlung-pecific DNA strand break and DNA-protein crosslinking.Chronicxposures to arsenic increase the incidence of skin,lung, bladdernd possibly liver cancer in human beings. Themolecularechanism of arsenic induced cancer is largely unknown,althoughnvolvement of free radicals has been suggested. Sincethe X-rayensitive Chinese hamster ovary cells, xrs-5 arealso o several free-radicals generating agents, including H2O2, we sed this cell line to test whether the genotoxiceffect of ediated via the generation of reactive oxygenspecies (ROS).he results indicate that the xrs-5 cells werealso more sensitive rsenite in terms of cell-killing andmicronuclei (MN) induction omparison to the parental CHO-K1cells. The level of arsenicptake and release, the levels ofelementary components forrsenic detoxification, such asglutathione, glutathione S-ransferase (GST), glutathionereductase (GSHR), superoxideismutase (SOD) were similar inthese two cell lines. Thectivities of catalase andglutathione peroxidase (GPx), however,ere 6- and 7-fold lower,respectively in the xrs-5 cells inomparison to the CHO-K1cells. Moreover, extra-cellular additionf Cat or GPx, couldeffectively reduce the frequency of arsenite-nduced MN.Pretreating CHO-K1 cells with mercaptosuccinate,n inhibitor ofGPx, enhanced the MN induction by arsenite and2O2.Simultaneous treatment with mercaptosuccinate and3-minotriazole, an inhibitor of Cat, synergisticallyincreased nduced MN. Furthermore, sodium selenium, astimulator of Gpxctivity, significantly reduced arsenite- and H2O2-induced MN.