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標題: | 六輕工業區周圍居民無機砷暴露之研究 Inorganic arsenic exposure of residents living near the No. 6 Naphtha Cracking Complex. |
作者: | Yi-Ting Hsieh 謝億廷 |
指導教授: | 詹長權(Chang-Chuan Chan) |
關鍵字: | 無機砷,砷甲基化,代謝體學,暴露評估, Inorganic arsenic,Arsenic methylation,Metabolomics,Petrochemical,Exposure assessment, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 台灣中部雲林地區之六輕石化工業區為台灣最大的工業區,該工業區被認為是台灣中部空氣污染物的主要排放源,其內部包含石油裂解廠、燃煤發電廠等,然而在過去研究中證實,石化工業與燃煤發電廠皆是重要的砷暴露來源,亦證實居住在六輕石化工業區周圍之居民尿中總砷含量較遠離工業區的居民高,且更在相關的流行病學研究報告指出該地區兒童哮喘與成人癌症等不良健康效應,但這些研究並沒有討論居民尿液中無機砷的暴露、代謝產物以及其可能導致的相關早期不良健康影響。因此,我們的研究目的是透過分析居民尿液中各砷物種之含量和代謝體學,來了解居住在六輕石化工業區周圍之老人與小孩的無機砷暴露、代謝情況以及早期不良健康指標。
我們的研究個案為2009 -2012年居住鄰近六輕石化工業區的 79 名老人 (>55歲) 與 81 名小孩 (9-15歲),收案內容包含尿液及生活習慣問卷調查,並限制至少居住在當地五年以上者,共 160 位,使用變異數分析以及 Chi-square test 進行研究目標之人口學統計分析。尿液樣本中砷物種分析使用 HPLC (High performance liquid chromatography, HPLC) 串聯 ICP-MS (Inductively coupled plasma mass spectrometry, ICPMS),共分析四種砷物種,分別為無機砷的As3+、As5+ 和有機砷的DMA (Dimethylarsinic acid, DMA)、MMA (Monomethylarsonic acid, MMA),並再利用肌酐酸(creatinine) 校正尿液濃度。我們使用三種砷物種之甲基化代謝指數,分別為主要甲基化指數 (Primary methylation index, PMI)、次要甲基化指數 (Secondary methylation index, SMI) 以及 (DMA+MMA)/(As3++As5+),其中 PMI 為 MMA 與 (As3++As5+) 之比值,而 SMI 為 DMA與 MMA 之比值,利用此三個指數來估算砷物種甲基化的程度。代謝體學資料運用線上統計軟體 MetaboAnalyst 4.0,來研究尿中砷物種暴露與各砷物種激化相關的特定代謝物之間的關聯。 我們的研究發現,在小孩組別當中,高暴露區的居民尿中無機砷 (As3++As5+ 總和) 濃度顯著高於低暴露區。在無機砷的百分比上,高暴露區也顯著高於低暴露區,而在老人組別當中,高暴露區居民尿中 As5+ 顯著高於低暴露區。砷物種甲基化指標顯示,小孩高暴露區相較低暴露組之 PMI 、有機砷與無機砷之比值顯著較低。而在老人組別當中,我們僅發現高暴露組之 PMI 顯著低於低暴露組。我們的研究也發現兒童高暴露組中,數個與無機砷相關甲基化途徑代謝物的下調,包括Glyceraldehyde-3-phosphate, Glutamic acid, Methionine, Glutaric acid, Fumaric acid, Glycine,我們亦發現與無機砷所造成體內氧化壓力上升之相關代謝體的上調,包括 2-keytrobutyric acid, L-Valine, Succinic acid, Hippuric acid, Serine。 本研究之結論為居住在六輕石化工業區附近的居民,其有較高的無機砷暴露,且相較於居住遠離六輕的居民,其無機砷的甲基化代謝效率較差,更在代謝體學資料中發現,與砷物種甲基化能力相關之代謝體下調以及與無機砷所造成體內氧化壓力相關之代謝體上調的情況。因此,統整以上,我們的無機砷暴露評估研究,提供了過去許多砷暴露之不良健康影響相關流行病學研究之重要證據。 The No. 6 Naphtha Cracker Complex in the Yunlin of central Taiwan is the largest industrial zone in Taiwan, which includes petrochemical complex and coal-fired power plants. Previous studies have confirmed that this industrial zone is the main arsenic exposure source in central Taiwan. Studies also found total urinary arsenic concentrations among residents living nears this industrial complex were comparatively higher that those living farther away from the complex. Adverse health effects reported in previous epidemiological studies in this area include children’s asthma and adult’s cancers. These studies, however, did not report exposures of inorganic arsenic, which is more toxic than organic arsenic, and metabolites of inorganic arsenic as well as early health effects. Our study objective is to know whether inorganic arsenics exposures can help explain adverse health effects among elderly and children near No. 6 Naphtha Cracker Complex by analyzing study subjects’ urinary arsenic species and metabolomics. Our study includes 160 subjects of 79 elderly (>55 years old) and 81 children (9-15 years old) residents living near No. 6 Naphtha Cracker Complex from 2009 to 2012. All of them have completed questionnaire surveys about living habits and factors related to exposure, and both of them lived in the local area at least five years. We used the variance analysis and Chi-square test to conduct demographic statistical analysis. Arsenic species in urine were analyzed by HPLC-ICPMS (High performance liquid chromatography-inductively coupled plasma mass spectrometry, HPLC-ICPMS) to differentiate four arsenic species, As3+, As5+, DMA (Dimethylarsinic acid, DMA), MMA (Monomethylarsonic acid, MMA), and reported as creatinine-adjust urine concentrations. We used three index, namely primary methylation index (PMI), secondary methylation index (SMI), and ratio of (DMA+MMA) /(As3++As5+), where PMI is the ratio of (DMA+MMA) to (As3++As5+ +DMA+MMA), and SMI is the ratio of DMA to (DMA+MMA) to estimate methylation metabolism of arsenic species. MetaboAnalyst 4.0 was used to investigate the association between urinary arsenic species exposure and specific metabolites associated with methylation of various arsenic species. Our study found that children’s inorganic arsenic concentrations, sum of As3+ and As5+, in the high exposure group were significantly higher than the low exposure group. The percentage of inorganic arsenic in total arsenics in the high exposure group was also significantly higher than low exposure group. By contrast, among the elderly, only As5+ concentrations were significantly higher for the high exposure group compared to the low exposure group. Arsenic methylation index showed that the children in high exposure group had lower PMI and the ratio of organic arsenic to inorganic arsenic than those in the low exposure group. As for the elderly, we only found lower PMI in the high exposure group compared to the low exposure group. We identified down-regulation of several inorganic arsenic-related methylation pathway metabolites, including Glyceraldehyde-3-phosphate, Glutamic acid, Methionine, Glutaric acid, Fumaric acid, Glycine showed among children in the high exposure group. We also found up-regulation of some metabolites of oxidative stress caused related to inorganic arsenic, including 2-keytrobutyric acid, L-Valine, Succinic acid, Hippuric acid, Serine. We conclude that residents living near the petrochemical complex have higher inorganic arsenic exposure and poorer methylation metabolism of inorganic arsenics than those living farther away. According to the study, the high exposure group had higher inorganic arsenic exposure than the low exposure group. Metabolites of methylation were downregulated while those of oxidative stress were upregulated among children with high inorganic arsenic exposures. Our refined exposure assessment provided evidence to support that inorganic arsenics played an important role of causing adverse health effects reported in previous epidemiological studies. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72644 |
DOI: | 10.6342/NTU201902217 |
全文授權: | 有償授權 |
顯示於系所單位: | 職業醫學與工業衛生研究所 |
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