隨著科技發展的進步，奈米物質獨特物化特性使其常被應用於各大工業，且具有極大的的發展空間。在食品工業中，奈米物質常作為一食品改良劑，使食品的品質進一步提升，例如：奈米氧化鋅（ZnO NPs）和奈米二氧化鈦（TiO2 NPs）分別被作為抗菌劑和增白劑來使用。但隨著奈米物質應用範圍擴大，使得人體暴露之途徑增加，故其獨特之物化特性對於人體之健康危害也逐漸被關注，但卻仍缺少相對應的風險評估方式。隨著大眾對動物福祉之意識提升，符合3R（替代、減少、優化）原則意念之體外試驗和電腦模擬方法，對於奈米物質毒性之危害風險評估更具前瞻性。因此，本研究目的為調查奈米顆粒之物化特性是如何造成基因毒性，並同時探討其毒性誘導機制。在細胞實驗中，使用具有不同化學組成及表面改質之羧酸奈米二氧化鈦（COOH-coated TiO2 NPs）、羧酸奈米氧化鋅(COOH-coated ZnO NPs)和胺基奈米氧化鋅（NH2-coated ZnO NPs）對HepaRG cells進行暴露。結果顯示，在HepaRG細胞中所有的奈米物質皆會在以不造成細胞毒殺效應之濃度範圍暴露下誘導基因毒性反應並使細胞存活率下降，同時也會使粒線體活性氧物質生成上升、膜電位下降及DNA損傷，促使細胞自噬和粒線體自噬作用。在三種奈米物質中，毒性強度由高至低依序為羧酸奈米氧化鋅、胺基奈米氧化鋅及羧酸奈米二氧化鈦。利用替代動物實驗方法探討奈米物質之潛在毒性風險是為現代研究極具前景之趨勢，本研究也應用替代動物毒性測試方法進行探討，並發現結果與先前動物模式之研究結果相符合，表明未來可依此作為符合3R原則之奈米物質毒性測試方法發展之基礎，同時，因奈米物質誘導之毒性機制仍未知，企盼未來能進行更深入的研究。

With the recent advances in technology, nanoparticles with their unique properties hold great promise in their current and future applications. In the food industry, the application of nanoparticles improves the quality of food products, e.g. ZnO NPs as anti-microbial additives and TiO2 NPs that serves as a whitening agent. Accordingly, different physicochemical properties of nanoparticles will lead to different characteristics. The increasing worldwide applications of nanoparticles in various fields have inevitably increased the risks of exposure to humans through various routes. Unfortunately, the rapid development is not accompanied by the respective risk assessment. Under the 3R principle (Replacement, Reduction, and Refinement), in vitro and in silico approaches are the alternative testing methods that are more suited to investigate nanoparticle-induced toxicity. Therefore, the purpose of this study is to investigate how the physicochemical properties of nanoparticles influence the resulting genotoxicity and the underlying mechanism. In this study, HepaRG cells were subjected to nanoparticles with different chemical composition and surface modification, which is COOH-coated TiO2 NPs, COOH-coated ZnO NPs, and NH2-coated ZnO NPs. All nanoparticles induced genotoxicity at a range of concentrations that is not cytotoxic in the cells, which were shown by the reduction in cell viability, increase in mitochondrial ROS production, MMP decrease, activation of DNA damage signaling pathway, and the induction of autophagy and mitophagy. Out of the three nanoparticles, COOH-coated ZnO NPs were found to be the most toxic, followed by NH2-coated ZnO NPs, and COOH-coated TiO2 NPs were the least toxic. The alternative toxicity testing methods for the analysis of nanoparticle-induced toxicity show a promising future. No experimental animals were used in this study, however, the results were consistent with the previous studies. Testing methods used in this study contribute to the validation of the alternative testing methods for nanoparticle toxicity studies. Further investigation of the nanoparticle-induced toxicity mechanism should be performed, as it remains to be elucidated.

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