三氯乙烯及四氯乙烯皆是易揮發性之有機溶劑，而經過GSH代謝過程時，會透過 GSH 結合轉變形成具有腎毒性和致腎癌性之代謝物。 本實驗研究的目標是要來確定GSH及p53蛋白質在三氯乙烯及四氯乙烯所誘導之肺臟毒性中所扮演之角色。人類肺臟癌細胞NCI-H460 (p53野生型) 之GSH濃度確實比NCI-H1299 (p53缺失)較低。本實驗結果顯示暴露在三氯乙烯或四氯乙烯之揮發氣體下，H460細胞內之過氧化氫濃度會有隨劑量上生而增加之趨勢；但H1299細胞則無明顯累積之現象。當細胞內過氧化氫濃度有累積之現象時，會伴隨著細胞嚴重損傷，就如同H460細胞會有明顯之脂質過氧化及細胞凋亡等現象，但H1299細胞則無明顯之增加現象。將H460細胞共同處理活性氧化物清除劑D-mannitol，Uric acid，及sodium selenite會明顯抑制三氯乙烯或四氯乙烯所誘導之脂質過氧化現象。相反地，H1299細胞前處理BSO，可以增加三氯乙烯或四氯乙烯所誘導之脂質過氧化現象。另外一方面，H460細胞處理三氯乙烯或四氯乙烯時，p53及Bax蛋白質也有增加之趨勢，且Bcl-2蛋白質有調降之情形。進一步結果顯示出，經三氯乙烯或四氯乙烯處理過後，細胞凋亡蛋白脢caspase-3之活性也有明顯增強之趨勢。總而言之，暴露於三氯乙烯或四氯乙烯之人類肺癌細胞，會經由GSH及p53參與而誘導細胞凋亡。 Both trichloroethylene (TCE) and tetrachloroethylene (PER) are volatile organic compounds and are converted to nephrotoxic and nephrocarcinogenic metabolites through GSH conjugation. The aim of this study was to elucidate the role of glutathione and p53 in TCE- and PER-induced lung toxicity. Human lung adenocarcinoma cells NCI-H460 (p53 wild type) was showed substantial lower level of GSH than NCI-H1299 (p53 null) cells. The results showed that exposure to vapor TCE and PER produced a dose-dependent accumulation of H2O2 in H460, but not in H1299 cells. The accumulation of H2O2 was accompanied by severe cellular damages, as indicating by the significant increase of lipid peroxidation and apoptosis in H460 cells, but not H1299 cells. Cotreatment of H460 cells with scavengers D-mannitol, Uric acid, and sodium selenite significantly attenuated the TCE- or PER-induced lipid peroxidation. The level of p53 and Bax proteins was elevated, while Bcl-2 protein was down-regulated in TCE- or PER-treated H460 cells. Furthermore, the activity of caspase-3, the apoptosis executioner, was also significantly enhanced in TCE- or PER-treated cells. In summary, the exposure of human lung cancer cells to TCE or PER can increase apoptosis through a GSH-mediated and a p53-dependent pathway.
