2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38041Humic substances are the most abundant natural compound and frequently found in the soil, sediments, water, coal, and other sources. They are heterogeneous highmolecular -weight organic compounds, and their composition varies in different geographic regions. Humic acids(HA) refer to the portion of humic substances dissolved in alkali, and they have many kinds of activated functional groups, bridge bonds and sponge network textures in HAmolecules. They can adsorb and complex a variety of metals, metallic oxides, salts, radioactive elements and some other non-metallic elements. Recent studies show that cell damage including oxidative DNA damage, NO release, apoptosis, growth retardation/cell transform, and free radicals release, lipid peroxidation may be induced by HA exposure. The mechanism of the cytotoxicity induced by HAmay be caused by the ability to reduce and release iron from ferritin storage which can disturb the redox balance and elicit oxidative stress within a biological system. Animal experiments have also shown the pathological changes of ending blood vessels in rats induced by HA are enhance by arsenic. In addition, the distribution pattern of HA correlated very well with the increased prevalence of organ diseases in the blackfoot disease endemic area, as reflected in epidemiological studies. It is hypothesized the HA-metal complexes, are possible etiological factors of disease such as goiter, hepatoma, bladder cancer, vascular disease and diabetes mellitus, and that free radicals are the common causative factor. Nowadays, it is still unclear that which of the compounds present in humic acid was responsible for the toxic effects observed. In our studies, the crude extracts of humic substances or HA will be further fractionated in order to determine the contribution of components responsible for the toxicity of cell or animals mutagenicity, and so on. In addition, when a representive metabolite of HA can be identified, we will try to demonstrate a suitable and specific DNA adduct for assessing the HA exposure.腐植質是廣泛分布於土壤、底泥、自然水體等環境介質的天然有機化合物， 具有複雜的高分子量雜環，且常隨著周圍環境的不同而有不同的組成。腐黑質、黃 腐酸及腐質酸是腐植質的主要組成成分之一，其中腐質酸可以溶於鹼性溶液中，本 身具有多種活性官能基團能夠吸附包括金屬或其氧化物、鹽類、放射性核種和其他 有機化合物如農藥、烷類等。最近的研究發現腐質酸能夠引發細胞產生包括DNA 氧 化、生長週期停頓、脂質過氧化、細胞轉型、自由基及一氧化氮上昇等傷害，在動 物實驗方面，亦有許多報告指出腐質酸會影響器官功能、末梢血管病變、肝臟過氧 化體增生、雄鼠睪丸萎縮等，尤其是砷和腐質酸共同暴露，對末梢血管之傷害更加 明顯。進一步探討其機制，目前有證據指出腐質酸會將ferritin 中的鐵還原成亞 鐵，並促使其釋出而擾亂生物體內之氧化還原平衡系統。 同時經過流行病學調查結果發現在烏腳病盛行地區常見之心血管病變、甲狀 腺腫、肝癌、膀胱癌、糖尿病等器官傷害標的與腐質酸或其代謝物在體內的分布相 當吻合，因此腐質酸在這些地方性疾病中之角色相當值得作進一步之研究與探討。 此外，由於腐植質是相當複雜之組合並廣泛分布於自然環境中，而且是重要的農業 用肥料與土壤改良劑，人們不可避免地會經常暴露於其中，但其對生物體之毒性作 用又有許多研究報告提出明確之證據，如何能夠建立相關的風險評估機制而得以取 其利而避其害就相當重要。鑑於腐植質之複雜特性及其對生態體系之影響，我們認 為應該由下面幾個方向作深入探討，包括中部地區及南部烏腳病盛行地區之腐植質 與金屬包括砷、鋁、鐵等環境流佈之基本背景資料及空氣氣懸微粒之腐植質可能分 佈；藉由環境採樣以及市售藥品等來源之腐植質或腐質酸作毒性評估，自由基反應 分析與螢光菌之毒性分析將扮演第一線之篩選角色，之後再行測試其細胞或動物毒 理作用。在此同時，對高毒性反應之樣品，我們將其作細部分離與純化工作，希望 藉此可以找到環境腐植質中之毒性化合物，並由此結構建立其代謝物包括DNA 加成 物之分析技術，提供日後在環境風險評估中之重要參考依據。另外對於腐質酸之結 構可能具有殺菌、抗病毒之功能亦有研究報告提出證據，在充分發揮腐植質的正面 價值考量下，我們也進行相關新藥或空氣濾材之研發工作，同時配合其他子計劃之 毒性篩選模式，亦能直接評估其安全性與實用價值。腐質酸重金屬環境毒物學Humic acidHeavy metalEnvironmental toxicologyProject