環境因子 (烹飪油煙) 致女性肺腺癌之基因體毒理與蛋白質體學研究

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學分子毒理學研究所 > 研究計劃 > Item 310902500/3346

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3346

Title:	環境因子 (烹飪油煙) 致女性肺腺癌之基因體毒理與蛋白質體學研究 Toxicogenomic and Proteomic Studies on Cooking Oil Fumes, an Environmental Risk Factor, Inassociation with Female Lung Adenocarcinoma
Authors:	林嬪嬪;張惠華;張雲菁;何佳琪 Pinpin Lin;Louis W. Chang;Yun-Ching Chang;Chia-Chi Ho
Contributors:	中山醫學大學毒理學研究所
Keywords:	肺癌;油煙 lung cancer;cooking oil fume
Date:	2005
Issue Date:	2010-12-17T03:05:32Z (UTC)
Abstract:	女性肺腺癌（FLAC）在台灣不僅是發生率高而且也佔婦女癌症死亡率之首位。流行病學證據顯示，在所有環境風險因子中，以烹飪油煙（COF）關係最為密切，而烹飪油煙中被認為造成癌症之主要成份為致突變劑tt-DDE及致癌物BaP。先前本實驗室研究證實，在人類支氣管上皮細胞株（BEAS-2B）長期處理tt-DDE（45天）會促進細胞增生，且因產生氧化僅迫使細胞激素表現量增加。近來，進一步發現長期處理tt-DDE會導致p27 mRNA及蛋白量降低，另外，再利用二種抗氧化劑（Vitamin C或NAC）分別與tt-DDE共同處理下，抑制tt-DDE之作用，使p27 mRNA及蛋白表達量回復趨於正常值。結果證實tt-DDE是經由氧化緊迫導致p27表現降低進而導致細胞增生。參考國家衛生研究院建立之女性肺腺癌基因體資料庫，發現在17位患者中有14位其p27之表達量亦降低，此結果與本實驗互相印證。慢性發炎被認為是癌化作用之早期指標，因此，我們擬探討BaP和E2調控發炎相關之基因表現。我們觀察到BEAS-2B細胞處理單獨BaP會導致數種細胞激素表現量增加，且在共同處理BaP和E2下, 數種細胞激素表現量愈高，另外，亦導致COX-2 mRNA的表現量和PGE2分泌量比單獨處理BaP的表現量高。由此證實，BaP和E2對促進發炎反應具有協同作用，但是其機制需要更深入的探討。綜合本計畫目前研究成果，我們證實烹飪油煙中兩種主要致癌或致突變物，tt-DDE and BaP, 於人類肺細胞中會改變某些與癌症發生初期相關之基因表現，而且雌性素會加強BaP改變這些基因表現之作用。由這些證據推測女性暴露烹飪油煙可能對肺細胞造成較大的影響，有利於肺細胞初期癌化的發生，而同時處理抗氧化劑可減緩tt-DDE的作用，因而建議攝取抗氧化劑可減少烹飪油煙對肺細胞之影響。我們將進一步探討如何阻斷BaP and 雌性素之交互作用，以減少女性暴露烹飪油煙所造成之傷害。 Female lung adenocarcinoma (FLAC) is not only unusually abundant; it is also the leading cause of cancer death among women in Taiwan. Among all potential environmental risk factors, cooking-oil fumes (COF) bear the most and strongest epidemiological evidence to be closely associated to the development of FLAC. The most concerning constituents in COF are perhaps BaP, a potent carcinogen, and tt-DDE (trans, trans-2,4-decadienal), a known mutagen. Previously we demonstrated that long-term treatment (45 days) with tt-DDE increased cell proliferation and cytokines secretion via oxidative stress in human bronchial epithelial cells BEAS-2B. Recently, we found that long-term treatment with tt-DDE significantly reduced p27 mRNA and protein levels, which was prevented by co-treatment with antioxidants, N-acetylcysteine and vitamin C. It appears that tt-DDE-induced oxidative tress contributed to p27 reduction, which may involve in the mechanism of tt-DDE-induced cell proliferation. Consistently, p27 mRNA levels were reduced in 14 out of 17 FLAC, comparing with paired non-tumor tissues (in the genomic database of FLAC generated by NHRI). We are examining effects of tt-DDE on expression of p27 related genes or proteins. Chronic inflammation is considered as the early event of carcinogenesis. Therefore, we investigated the interaction between BaP and 17-beta estradiol (E2) on expression of inflammation-related genes. BaP alone significantly induced several cytokines expression in BEAS-2B cells. Co-treatment with E2 potentiated BaP-induced cytokines expression in BEAS-2B cells. Furthermore, the combination of BaP and E2 significantly increased cyclooxygenase 2 mRNA levels as well as prostaglandin E2 secretion in BEAS-2B cells. These data suggest that BaP and E2 synergistically enhance inflammatory response in the lung epithelial cells. The mechanism is under investigation.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3346
Appears in Collections:	[醫學分子毒理學研究所] 研究計劃

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