Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/5002
標題: 運用血紅蛋白胼合物為生物指標評估多環芳香族碳氫化合物之環境暴露與體內累積之雌性激素醌類代謝物相關性之研究
Investigation of the association of environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and cumulative body burden of estrogen quinones in breast cancer patients using hemoglobin adduct as biomarkers
作者: 蘇弘傑
Su, Hung-Chieh
關鍵字: Hemoglobin
雌性激素
Estrogen
Naphthalene
Quinone
Protein adduct
萘醌蛋白質胼合物
出版社: 環境工程學系所
引用: 洪佩慈 (2009) 探討雌性激素受體與芳香族碳氫化物受體間訊息傳遞之交互作用。國立中興大學環境工程研究所碩士論文,台灣台中。 陳有宏 (2010) 替代金紙焚化對多環芳香烴化合物減量效益之評估。嘉南藥理科技大學碩士論文,台灣台南。 彭麗珠 (2010) 台灣中部地區大氣中粒狀污染物之多環芳香烴化合物分佈特性之研究。國立中興大學環境工程研究所碩士論文,台灣台中。 楊宗洲 (2010) 運用蛋白質胼合物為生物指標評估多環芳香族碳氫化合物及戴奧辛之環境暴露對雌性激素之活性醌類代謝物累積組之劑量之影響。國立中興大學環境工程研究所碩士論文,台灣台中。 魏子翰 (2009) 同步分析人類血清白蛋白中萘及雌性激素醌類代謝物之蛋白質胼合物。國立中興大學環境工程研究所碩士論文,台灣台中。 劉致辰 (2011) 探討乳癌病患身體質量指數及雌性激素代謝活化基因之多型性與白血球去鹼基核酸背景值之相關性。國立中興大學環境工程研究所碩士論文,台灣台中。 林慶全 (2011) 運用血清白蛋白胼合物為生物指標探討體內累積之雌性激素-3,4-苯醌代謝物作為乳癌風險預測指標之研究。國立中興大學環境工程研究所碩士論文,台灣台中。 Alexandra, 2010. Protein Adducts As Prospective Biomarkers of Nevirapine Toxicity. Bagchi, D., Bagchi, M., Balmoori, J., Vuchetich, P.J., and Stohs, S.J., 1998. Induction of oxidative stress and DNA damage by chronic administration of naphthalene to rats, Res.Commun.Mol.Pathol.Pharmacol. 101,249-257. Bagchi, M., Balmoori, J., Ye, X., Bagchi, D, ., R., S.D. and Stohs, S.J. , 2001. 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Cancer Epidemiol Biomarkers Prev 9, 147-150.
摘要: 17β-雌二醇-2,3-醌類代謝物 (E2-2,3-Q) 和17β-雌二醇-3,4-醌類代謝物 (E2-3,4-Q) 以及1,2-NPQ和1,4-NPQ為雌性激素與萘之活性代謝產物,並且雌性激素與萘被認為會誘發遺傳毒性。本研究目的為建立一種方法來同步偵測雌性激素與萘之醌類蛋白質胼合物並分析量測台灣女性乳癌病患 (n=85) 的血紅蛋白胼合物背景值。從體外實驗結果證實,血紅蛋白之雌性激素醌類胼合物含量會隨著雌性激素醌類添加的濃度增加而增加。時間效應實驗證明,無論是E2-2,3-Q和E2-3,4-Q的胼合物都會迅速在10分鐘到達最大鍵結量並且能維持長達24小時。研究分析乳癌病患 (n=85) 之血紅蛋白的雌性激素及萘之醌類胼合物之背景值,其E2-2,3-Q-4-S-Hb、E2-3,4-Q-2-S-Hb、1,2-NPQ-Hb、1,4-NPQ-Hb結果之中間值分別為495 (範圍281-764)、992 (範圍700-1508)、272 (範圍33.0-709)及32.0 (範圍12.0-79.0) (pmole/g)。相關性分析結果顯示,經由對數轉換之平均值E2-2,3-Q-4-S-Hb與E2-3,4-Q-2-S-Hb有顯著相關 (r=0.643, p<0.001)。另外,1,2-NPQ-Hb與1,4-NPQ-Hb亦有顯著相關 (r=0.549, p<0.001),而在乳癌病患年齡小於50歲時1,2-NPQ-Hb與E2-2,3-Q-4-S-Hb有顯著相關 (r=0.505, p<0.001)以及E2-3,4-Q-2-S-Hb (r=0.345, p<0.001)皆具有正相關性。總體來說,結論是多環芳香族碳氫化合物之累積組織劑量可能會提高雌性激素醌類的活化而且此研究方法的開發可應用於流行病學上評估雌性激素體內平衡之生物標誌。
Both 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q) and 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) are reactive metabolites of estrogen and naphthalene that are thought to be responsible for the estrogen and naphthalene-induced genotoxicity. The aim of this study was to establish a methodology to simutaneously analyze both estrogen and naphthalene quinone-derived protein adducts and to measure the background levels of these adducts in human hemoglobin (Hb) derived from female breast cancer patients (n=85) in Taiwan. Results from in vitro studies confirmed that the production of estrogen quinone-derived adducts on Hb increased with increased concentration of estrogen quinones. Time-course experiments suggested that both E2-2,3-Q- and E2-3,4-Q-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter for up to 24 h. When we investigated the levels of estrogen and naphthalene quinone-derived adducts in human hemoglobin, cysteinyl adducts of E2-2,3-Q-4-S-Hb, E2-3,4-Q-2-S-Hb, 1,2-NPQ-Hb, and 1,4-NPQ-Hb were all detected in breast cancer patients (n=85) with median levels at 495 (range 281-764), 992 (range 700-1508), 272 (33.0-709), and 32.0 (12.0-79.0) pmol/g, respectively. Levels of E2-2,3-Q-4-S-Hb correlated significantly with those of E2-3,4-Q-2-S-Hb (correlation coefficient r=0.643, p<0.001). Similarly, levels of 1,2-NPQ-Hb correlated significantly with those of 1,4-NPQ-Hb (r=0.549, p<0.001). We noticed that levels of 1,2-NPQ-Hb positively correlated with those of E2-3,4-Q-2-S-Hb (r=0.505, p<0.001) and E2-2,3-Q-4-S-Hb (r=0.345, p<0.001) in patients with ages less than 50. Overall, this evidence suggests that cumulative body burden of polycyclic aromatic hydrocarbons may enhance bioactivation of estrogen to the reactive quinone species and that the methodology developed in this study may be applied to epidemiological studies as biomarkers of estrogen homeostasis.
URI: http://hdl.handle.net/11455/5002
其他識別: U0005-1808201123543100
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1808201123543100
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