多溴二苯醚之生物脂肪累積性及後代基因毒性影響

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Title:	多溴二苯醚之生物脂肪累積性及後代基因毒性影響 Bioaccumulation of Polybrominated Diphenyl Ethers in Adipose Tissue and Epigenetic Toxicity in Offsprings
Authors:	宋鴻樟;莊淳宇
Contributors:	中國醫藥大學環境醫學研究所
Date:	2010-07
Issue Date:	2010-09-02 18:52:16 (UTC+8)
Abstract:	環境荷爾蒙(內分泌干擾物質)為一種外因性物質或混合物，會改變內分泌系統的功能，因此對生物個體及其後代或族群會造成不良的健康影響。多溴二苯醚(polybrominated diphenyl ethers; PBDEs)是一種內分泌干擾物質，與雌激素受體間具有親和力，為防火材質中之阻燃劑，廣泛用在日常生活用品中，如傢俱和天花板。PBDEs流佈在環境中，在土壤、空氣、底泥、鳥類、水生生物、魚類、粉塵、人體組織和母乳中可被偵測到。飲食和家中粉塵是一般民眾主要的暴露途徑，另外職業暴露也是不可忽視的一環。由於PBDEs為一持久性有機污染物(persistent organic pollutants)，會累積於生物體脂肪細胞中，脂肪細胞所分泌的脂肪激素(adipokine)與正常生物體能量代謝、內分泌系統和免疫調控有關。由於PBDEs會影響生物體內分泌系統， adipokine中的瘦脂素(leptin)和脂聯素(adiponectin)受到下視丘的調控來調節甲狀腺功能，若是生物體暴露到PBDEs累積在脂肪組織中，可能會影響adipokine 生成進而影響體內恆定。此外，基因可透過基因外調節系統(epigenetics)來調節基因表現，此為不改變DNA序列情況下，經由改變基因表現來影響基因功能， DNA甲基化是基因外調節的一種，環境因素所誘導的DNA甲基化會遺傳對後代造成影響。因此本研究將探討PBDEs暴露後累積在生物脂肪組織中所造成之脂肪激素，如脂瘦素和脂聯素，蛋白質分泌和其基因甲基化影響之關連性，並透過動物實驗觀察PBDEs的世代健康效應。此計畫之研究目的為： 1. 探討脂肪細胞株暴露PBDEs，脂肪激素基因甲基化之情形。 2. 探討大鼠暴露PBDEs，脂肪激素－脂瘦素和脂聯素蛋白質分泌和基因甲基化之程度。 3. 探討懷孕母鼠暴露PBDEs，對幼鼠造成之世代健康效應。 The endocrine disruptor is an exogenous substance or a mixture of related chemicals that may alter the function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, its progeny or (sub)populations. Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants used in a variety of consumer products. PBDEs have become ubiquitous environmental contaminants. They have been detected in soil, air, sediments, birds, marine species, fish, house dust, and human tissues, blood and breast milk. Diet and house dust appear to be the major sources of PBDE exposure in the general population, though occupational exposure can also occur. Because of the persistent nature, this organic pollutant PBDEs is able to accumulate in adipose cells of biological organisms. Adipokines secreted from adipose cells regulate energy metabolism, endocrine system and immune homeostasis. Several reports have indicated that adipokines, such as leptin and adiponectin, regulate thyroid function at the hypothalamic-hypophyseal level. The biological organisms exposed PBDEs and its accumulation in adipose tissue might affect the adipokinegenesis resulting unbalanced homeostasis. Epigenetics can transmit the information of genome stability without the change of DNA sequence. DNA methylation is an epigenetic event that affects the cell function by the altering gene expression and important regulator of gene transcription. The DNA methylation induced by environmental factors might be inherited to offspring and change the gene expression. This study will investigate the association between PBDEs exposure and adipokines gene methylation, and using animal model to evaluate the bioaccumulation in the adipose tissue and the consequence of offspring health effect. There are three specific aims proposed for this study: Aim 1: To investigate the characteristics of DNA methylation of leptin and adiponectin genes in PBDEs-exposed adipose cell line. Aim 2: To investigate the association between protein secretion of leptin and adiponectin and their DNA methylation in PBDEs-exposed rats. Aim 3: To evaluate the health effect on offspring rats potential from pregnant PBDEs-exposed rats.
Appears in Collections:	[Graduate Institute of Environmental Medicine] Research reports

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