臺灣博碩士論文加值系統

本研究目的探討尚在飲用地下水的蘭陽盆地居民，暴露於高濃度的無機砷下，其無機砷代謝能力之分布。硒為人體必須金屬，亦具抗氧化作用。動物、體外試驗及流行病學研究中發現硒對無機砷有拮抗作用。因此本研究同時探討蘭陽盆地的居民其血清及尿液中總硒量與無機砷甲基化代謝能力之間的相關性。
民國八十年設籍於當地40歲以上之居民12000人中參與問卷訪視者共計8102人，依飲用地下水砷暴露濃度分組隨機選取317人為研究對象。收集研究對象所飲用之井水及尿液儲存於-200 C，血液儲存於-700 C冰庫中。以感應耦合電漿－原子發射光譜分析法測定井水砷濃度，以石墨爐式原子吸收光譜儀測定血清中總硒量以及尿液中總硒量與總砷量，利用高效能液相層析儀連結氫化器原子吸收光譜儀測定尿液中的無機砷甲基化代謝物種，並以統計軟體進行統計分析。
結果發現性別、抽煙或飲酒與否與慢性砷暴露指標(飲用含砷井水年數，飲用井水含砷濃度，累積砷暴露量)均沒有顯著差異。男性的單甲基砷酸百分比及總砷量比女性顯著偏高而雙甲基砷酸百分比卻比女性顯著偏低。未飲酒者其無機砷百分比較飲酒者低而雙甲基砷酸百分比較飲酒者偏高。年齡小於51歲者其血清硒濃度比58至64者者顯著偏高。男性的尿液硒及砷濃度比女性偏高，未抽菸者尿液硒及砷濃度比抽菸者為低。在調整年齡與性別後，井水含砷濃度越高者則總砷量及尿液砷濃度越高；累積砷暴露量越高則總砷量越高。在調整年齡與性別及其他危險因子後，血清維生素E越高則尿液砷濃度與總砷量越高；無機砷百分比隨尿液硒濃度增加而顯著減少，雙甲基砷酸百分比隨尿液硒濃度增加而顯著增加。尿液硒似乎會使砷甲基化代謝能力增加，此須進一步探討。

The objective of this study was to discuss the distribution of the inorganic arsenic metabolism capabilities among residents of Lanyang Basin who drank underground water and exposed to high concentrations of inorganic arsenic. Selenium is a trace essential elements that is important in providing protection against oxidative damage. It was observed selenium produced antagonism against inorganic arsenic at animals, in vitro experiments and epidemiology studies. Therefore, we also discussed the relationship between total selenium levels in serum and urinary arsenic methylation capabilities among the residents in Lanyang Basin.
At 1991, 8,102 residents were participated questionnaire interview. According to the arsenic concentration of their drinking water, they were classified into two groups(less or equal to 50 ug/L and over ug/L); from each group, totally 317 persons were randomly sampled. Their drinking well water, urine, and blood were collected and stored in refrigerators at the temperature of -20oC and —70oC respectively. The concentration of arsenic in well water, the total selenium levels in serum, total selenium and arsenic levels in urine, and inorganic arsenic methylation species in urine were determined by inductively coupled plasma atomic emission spectroscopy, graphite furnace atomic absorption spectrometry, and high-performance liquid chromatography with hydride generation atomic absorption spectrometry respectively. The results were analyzed by statistical software.
It turned out no differences in chronic arsenic exposure index (the number of years of drinking arsenic well water, the concentration of arsenic of well water, cumulative arsenic exposure) among opposite genders, cigarette smoking or not, and alcohol drinking or not. The percentage of monomethylarsonic acid and the total arsenic levels in male were significantly higher than those in female, but the percentage of dimethylarsinic acid in male were significantly lower than those in female. The percentages of inorganic arsenic in non-alcohol drinkers were lower than those in alcohol drinkers, but the percentage of dimethylarsinic acid in non-alcohol drinkers were higher than those in alcohol drinkers. The concentration of selenium in serum of the residents below 51 years old were significantly higher than those of the residents between 58 and 64 years old. The concentrations of arsenic and selenium in urine in male and smoker were higher than those in female and non-smokers respectively. After adjusting the age and gender, the higher the concentration of arsenic in well water, the higher the total arsenic levels and the concentration of the arsenic in urine; the higher the cumulative arsenic exposure in drinking water, the higher the total arsenic levels in urine. After adjusting the age, gender, and other risk factors, the higher the concentration of Vitamin E in serum, the higher the concentration of the arsenic and total arsenic levels in urine. The percentage of inorganic arsenic significantly decreased while the concentration of selenium in urine increased; the percentage of dimethylarsinate significantly increased while the concentration of selenium in urine increased. It seemed the selenium in urine would increase the metabolism of methylation of arsenic, this needed further investigation.

中文摘要…………………………………………………….I
英文摘要…………………………………………………….II
目錄………………………………………………………… III
表目錄………………………………………………………V
圖目錄………………………………………………………VII
第一章 前言…………………………………………….…1
第二章 文獻探討………………………………………….4
第一節 砷的特性與環境流佈…………………….…4
第二節 砷的毒性………………………………….…5
第三節 砷的代謝………………………………….…6
第四節 硒的特性與環境流佈………………….…...16
第五節 硒的功能……………………………………17
第六節 硒的毒性……………………………………17
第七節 硒的代謝……………………………………18
第八節 砷和硒的交互作用…………………………19
第九節 其他影響砷代謝的因子……………………23
第三章 材料與方法………………………………………25
第一節 研究對象的選取……………………………25
第二節 基本資料的取得與檢體的測定……………25
第四章 結果………………………………………………36
第一節 社會人口學基本資料………………………36
第二節 慢砷暴露指標之分布………………………37
第三節 砷代謝物種及代謝能力之分布……………38
第四節 血清微量營養素之分布……………………40
第五節 血清硒、尿液硒及砷濃度之分布…………41
第六節 依血清脂值指標及井水砷濃度標準分組
對無機砷甲基化代謝能力，血清與尿液
硒濃度及尿液砷濃度之影響……………..42
第七節 血清硒、尿液硒及砷濃度與砷代謝能
力指標與危險因子之單變項迴歸分析…..45
第八節 尿液硒及砷濃度、總砷量與砷代謝
能力指標之多變項分析…………………..52
第九節 以飲用水含砷濃度分組之多變項分析…..58
第五章 討論……………………………………………..61
參考文獻…………………………………………………..66
附錄一 宜蘭縣飲用地下水地區居民健康調查問卷
附錄二 宜蘭縣地下水高砷地區居民健康狀態追蹤
訪視問卷

1.Tseng WP,Chu HM,How SW,Fong JM,Lin CS and Yeh S. Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. Journal of the National Cancer Institute 1968;40:453-63.
2.Wu HY,Chen KP,Tseng WP,and Hsu CL. Epidemiologic studies on blackfoot disease. 1. prevalence and incidence of this disease by age,sex,year,occupation and geographical distribution. In: Memmoris, College of Medicine, National Taiwan University. Taipei: National Taiwan University National Taiwan University 1961;7:33-50.
3.Chen CJ and Wang CJ. Ecological correlation between in well water and age-adjusted mortality from malignant neoplasms. Cancer Research 1990;50:5470-4.
4.Tseng WP. Effects and dose-response relationship of skin cancer and blackfoot disease with arsenic. Environmental Health Perspectives 1977;19:109-19.
5. Vahter M. Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environmental Research 1981;25:286-93.
6.Marafante E, Vahter M, and Envall J. The role of the methylation in the detoxication of arsenate in the rabbit. Chemico-Biological Interactions, 1985;56:225-38.
7.Marafante E, and Vahter M Solubility, retention, and metabolism of intratracheally and orally administered inorganic arsenic compounds in the hamster. Environmental Research 1987;42:72-82.
8.Vahter M, Couch R, Nermell B, and Nilsson R Lack of methylation of inorganic arsenic in the chimpanzee. Toxicology and Applied Pharmacology 1995;133:262-8.
9.Zakharyan RA, Wildfang E, and Aposhian HV Enzymatic methylation of arsenic compounds. Toxicology and Applied Pharmacology 1996;140:77-84.
10.Healy SM, Zakharyan RA, Aposhian HV. Enzymatic methylation of arsenic compounds: IV. In vitro and in vivo deficiency of the methylation of arsenite and monomethylarsonic acid in thy guinea pig. Mutation Research 1997;386:229-39.
11.Hopenhayn-Rich C, Biggs ML, Smith AH, Kalman DA,and Moore LE. Methylation study of a population environmentally exposed to arsenic in drinking water. Environmental Health. Perspectives 1996;104:620-8.
12.Hopenhayn-Rich C,Biggs ML, Kalman DA, Moore LE, and Smith AH. Arsenic methylation pattens before and after changing from high to lower concerntrations of arsenic in drinking water. Environmental Health Perspectives 1996;104:1200-7.
13.Hsueh YM, Huang YL, Huang CC, Wu WL, Chen HM, Yang MH, Lue LC, and Chen CJ. Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniass-hyperendemic area in Taiwan. Journal of Toxicology and Environmental Health, Part A 1998;54:431-444.
14.Lin TH, Huang YL, and Wang MY. Arsenic species in drinking water, hair, fingernails, and urine of patients with blackfoot disease. Journal of Toxicology and Environmental Health, Part A 1998;53:85-93.
15.Concha G, Nermell B,and Vahter M. Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina. Environmental Health Perspectives 1998;106:355-9.
16.Kurttio P,Komulainen H,Hakala E, KahelinH, Pekkanen J. Urinary excretion of arsenic species after exposure to arsenic present in drinking water. Archives of Environmental Contaminative Toxicology 1998;34:297-305.
17.Vahter M, Concha G, Nermell B, Nilsson R, Dulout F, Natarajan AT. A unique metabolism of inorganic arsenic in native Adean women. European Journal of Pharmacology Environmental Toxicology and Pharmacology Section 1995;293:455-62.
18. Barceloux DG. Selenium. Clinical Toxicology 1999;37(2):145-72.
19.Spallholz JE: On the nature of selenium toxicity and carcinostatic activity. Free Radical Biological and Medicine 1994;17:45-64.
20..Hilmy AM,. El-Domiaty NA, Kamal MA, Mohamed MA and Abou Samra WE. Effect of some arsenic antagonists on the toxicity,distribution and excretion of arsenite and arsenate in rats. Comparative Biochemistry and Physiology 1991;99C:357-62.
21.Biswas S, Talukder G, Sharma A. Prevention of cytotoxic effects of arsenic by short-term dietary supplementation with selenium in mice in vivo. Mutation Research 1999;441:155-60.
22.Berry JP, Galle P. Selenium- arsenic interation in renal cells: role of lysosomes. Electron microprobe study. Journal of Submicroscopic Cytological Pathology 1994;26:203-10.
23.Ueda H, Kuroda K and Endo G. The inhibitory effect of selenium on induction of tetraploidy by dimethylarsinic acid in Chinese hamster cells. Anticancer Research 1997;17:1939-44.
24.Styblo M.,and Thomas DJ In vitro inhibition of glutathione reductase by arsenotriglutathione. Biochemistry Pharmacology 1995;49:971-7.
25.Kenyon EM and Hughes MF. Influence of dietary selenium on the disposition of arsenate in the female B6C3F1 mouse. Journal of Toxicology and Environmental Health 1997;51:279-99.
26.Merck & Co.,INC. The Merck Index.1996;12th ed.:134-5.
27.Yeh S, How SW and Lin CS. Arsenical cancer of skin. Cancer 1968;21:312-29.
28.Browon SM and Ranowitz AD. The precursors of cutaneous squamous cell carcinoma. International Journal of Dematology 1979;18:1-16.
29.EPA. Health Effects Assessment for Arsenic. Washington, DC: Environmental Protection Agency, Office of Emergency and Remedial Response. EPA/540/1-86/020,1984.
30.Mizuta N, Mizuta M, Ita F,et al. An outbreak of acute arsenic poisoning caused by arsenic-contaminated soy sause(shoye). A clinical report of 220 cases. Bull Yamaguchi Med Sch 1956;4:131-50.
31.Hamamoto E. Infant arsenic poisoning by powdered milk. Japanese Medical Journal 1955;1649:2-12.
32.Borgono JM,Vincent P,Venturino H and Infante A. Arsenic in the drinking water of the City of Antofagasta: Epidemiological and clinical study before and after the intallation of the treatment plant. Environmental Health Perspectives 1977;19:103-5.
33.Cebrian ME.1987. Some potential problems in assessing the effects of chronic arsenic poisoning in North Mexico. In:Preprints of papers presented at the American Chemical Society,Division of Environmental Chemistry,194th Meeting,pp.114-6.
34.Welch K,Higgins I,Oh,M and Burchfiel C. Arsenic exposure,smoking,and respiration cancer cancer in copper smelter workers. Archives of Environmental Health. 1982;37:325-35.
35.Wingren G,and Axelson O. Mortality in the Swedish glassworks industry. Scandinavian Journal Work Environmental and Health 1987;13:412-6.
36.Gustavsson P, Gustavsson A. and Hogstedt C. Excess mortality among Swedish chimney sweeps. Journal of Industrial Medicine 1987;44:738-43.
37.Chiou HY,Huang WI, Su CL, Chang SF, Hsu YH, Chen CJ. Dose-response relation between prevalence of cerebrovascular disease and ingested inorganic arsenic. Stroke 1997;9:1717-23.
38.Hutchinson J. Arsenic cancer. British Medical Journal 1887;2:1280-81.
39.World Health Organization. IARC monographs on the evaluation of the carcinogenic risk of chemical to humans:Some metal and metallic compounds. Lyon:International Agency for Research on Cancer,1980.
40. International Agency for Research on Cancer. Evaluation of carcinogenic risks to humans, Supplement 7, Lyon. International Agency for Research on Cancer, 1987;100-106.
41.Lee AM and Fraumeni JFJR. Arsenic and respiratory cancer in man: A occupational study. Journal of National Cancer Institute 1969;42:1045-52.
42.Chen CJ,Chuang YC,Lin TM,and Wu HY. Malignant neoplasms among residents of a blackfoot disease endemic area in Taiwan :high arsenic artesian well water and cancers. Cancer Research 1985;45:5895-9.
43.Chiou HY,Hsueh YM.Liaw KF,Horng SF,Ching MH,Pu YS,Lin J S-N,Huang CH and Chen CJ. Incidence of internal cancers and ingested inorganic arsenic: A seven-year follow-up study in Taiwan. Cancer Research 1995;55:1296-1300.
44.Buchet JP and Lauwerys R. Study of inorganic arsenic methylation by rat liver in vitro:relevance for interpretation of observation in man. Archives of Toxicology 1985: 57:125-31.
45.Healy SH, Casarez EA, Ayala-Fierro F, and Aposhian HV. Enzymatic methylation of arsenic compounds: V arsenite methyltransferase activity in tissues of mice. Toxicology and Applied Pharmacology 1998;148:65-70.
46.Robert A. Zakharyan and H. Vasken Aposhian. Enzymatic reduction of arsenic compounds in mammalian systems: The rate-limiting enzyme of rabbit liver arsenic biotransformation is MMAV reductase. Chemical Research in Toxicology 1999;12:1278-83.
47.Styblo M,Yamauchi H, and Thomas DJ. Comparative in vitro methylation of trivalent and pentavalent arsenicals. Toxicology and Applied Pharmacology 1995;135:172-8.
48.Styblo M,Delnomdedieu M, Thomas DJ. Mono- and dimethylation of arsenic in rat liver cytosol in vitro. Chemico-Biological Interactions1996;99:147-64.
49.Hall L, George SE, Kohan MJ, Styblo M, and Thomas DJ. In vitro methylation of inorganic arsenic in mouse intestinal cecum. Toxicology and Applied Pharmacology 1997;147:101-9.
50.Moore MM,Harrington-Brock K,Doerr CL. Relative genotoxic potency of arsenic and its methylated metabolites. Mutation Research 1997;386:279-90.
51.Buchet JP, Lauwerys R and Roles H. Comparsion of the urinary excretion of arsenic metabolites after a single dose of sodium arsenite, monomethyl arsonate, or dimethyl arsinate in man. International Archives of Occupation Environmentmental Health, 1981a;48:71-9.
52.Farmer JG, Johnson LR. Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic. British Journal of Industrial Medicine 1990;47:342-8.
53.Hakala E, Pyy L. Assessment of exposure to inorganic arsenic by determining the arsenic species excrete in urine. Toxicology Letters 1995;77:249-58.
54.Yager JW, Hicks JB,and Fabianova E. Airborne arsenic and urinary excretion of arsenic metabolites during cleaning operations in a Slovak coal-fired power plant. Environmental.Health Perspectives 1997;105:836-42.
55.Apostoli P, Alessio L, Romeo L, Buchet JP, Leone R. Metabolism of arsenic after acute occupational arsenic intoxition. Journal of Toxicology and Environmental Health 1997;52:331-42.
56.Benramdane L, Accominotti M, Fanton L, Malicier D, and Vallon JJ. Arsenic speciation in human organs following fatal arsenic trioxide poisoning －A case report. Clinical Chemistry 1999;45(2):301-6.
57.Merck & Co.,INC. The Merck Index.1996;12th ed.:1448-9.
58.Simonoff M:Selenium in food and nutrition in France. Selenium in Medicine and Biology. 15-20,1988.
59.Rotruck JT, Pope AL,Ganther HE,S wanson AB, Hafeman DG, Hoekstra WG: Selenium:Biochemical role as a component of glutathione peroxidase. Science 1973; 269:588-90.
60.Franke: A new toxicant occuring naturally in certain samples of plant foodstuffs. Journal of Nutrition 1934;8:597-608.
61.Schwarz K,Foltz CM: Selenium as an intergral part of factor 3 against dietary necrotic liver degeneration. Journal of American Chemical Society 1957;79:3292.
62.Valentine JL, Cebrian ME, Garcia-vargas GG, Faraji B, Kuo J, Gibb HJ, and Lachenbruch PA. Daily selenium intake estimates for residents of arsenic-endemic areas. Environmental Research 1994;64:1-9.
63.Tsalev DL, Zaprianov ZK. Atomic Absorption Spectrometry in Occupational and Environmental Health Practice. 1983 Volume I p182-187 CRC Press Inc Boca Raton, Florida.
64.Hoffman JL and McConnell KP. Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite. Archives of Biochemistry and Biophysics 1987;254:534-40.
65.Wester PO, Brune D, and Nordberg G. Arsenic and selenium in, liver, and kindey tissue from dead smelter workers. British Journal of Industrial Medicine. 1981;38:179-84.
66.Hu GG. Investigation of protective effect of selenium on genetic materials among workers exposed to arsenic. Chinese Journal of preventive Medicine. 1989;23(5):286 -8.
67.Babish H, Martin-Alguacil N and Borenfreund E. Arsenic-selenium interactions determined with cultured fish cells. Toxicology Letters 1989;45:157-64.
68.Glattre E, Mravcova A, Lener J, Vobecky M, Egertova E,and Mysliveckova M. Study of distribution and interaction of arsenic and selenium in rat thyroid. Biological Trace Element Research 1995;49:177-86.
69.Wang CT, Chang WT, Huang CW, Chou SS, Lin CT, Liau SJ, Wang RT. Study on the concentrations of arsenic, selenium, copper,zinc and iron in the hair of blackfoot disease patients in different clinical stages. European Journal of Clinical Chemistry Clinical Biochemistry 1994;32(3):107-11.
70.Wang CT. Concentration of arsenic, selenium, zinc, iron and copper in the urine of blackfoot disease patients at different clinical stages. European Journal of Clinical Chemistry Clinical Biochemistry 1996;34:493-97.
71.Raie RM. Regional variation in As, Cu, Hg, and Se and interaction between them. Ecotoxicology and Environmental Safety 1996;35:248-52.
72.Buchet JP,Geubel A., Pauwels S., Mahieu P. and Lauwerys R. The influence of liver disease on the methylation of arsenic in humans. Archives of Toxicology 1984: 55:151-4.
73.Le XC, Cullen WR, and Reimer KJ. Human urinary arsenic excretion after one-time ingestion of seaweed, crab, and shrimp. Clinical Chemistry 1994;40:617-24.
74.Vahter M and Marafante E :Effects of low dietary intake of methionine, choline or proteins on the biotransformation of arsenite in the rabbit. Toxicology. Letter. 1987;37:41-46.
75.Ma MS and Le XC. Effect of arsenosugar ingestion on urinary arsenic speciation. Clinical Chemistry 1998;44:3:539-50.
76.許妙甘，健康居民砷代謝能力與飲食習慣之相關性研究（初步研究），台北醫學院大專學生參與專題研究計畫成果報告，1999年6月。
77.魏敏澧，蘭陽盆地居民飲用之地下水中無機砷及其他元素含量與癌症發生之相關性研究，台北醫學院藥學研究所碩士論文，1998年6月。
78.陳吳詮，蘭陽盆地居民血清中微量營養元素對頸動脈粥狀硬化危險性之相關性研究，台北醫學院公共衛生學研究所碩士論文，1999年6月。
79.簡淑婷，非砷暴露地區健康居民砷代謝能力及其影響因子之相關性研究（初步研究），台北醫學院大專學生參與專題研究計畫成果報告，2000年2月。
80.Yamauchi H, Takahashi K, Mashiko M, and Yamamura Y. Biological monitoring of arsenic exposure of gallium arsenide and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair. American Industrial Hygiene Association Journal. 1989;50:606-12.
81.Garland M, Morris JS, Rosner BA, Stampfer MJ, Spate VL, Baskett CJ, Willett WC, and Hunter DJ. Toenail trace element levels as biomakers:reproducibility over a 6-year period. Cancer Epidemiology, Biomarkers and Prevetion 1993;2:493-7.
82.Navarro-Alarcon M, Serrana HLG, Perez-Valero V, Lopez- Martinez C. Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus. The Science of the Total Environmental 1999;228:79-85.
83.Horng CJ,Tsai JL, and Lin SR. Determination of urinary arsenic, mercury, and selenium in steel production workers. Biological Trace Element Research 1999;70:29-40.
84.Coudray C, Roussel AM, Arnaud J, Favier A, and EVA study group. Selenium and antioxidant vitamin and lipidoperoxidation levels in preaging French population. Biological Trace Element Research 1997;57:183-90.