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日本琵琶湖野生普通鸬鹚中二噁英类化合物对肝脏CYP1A的诱导作用、同类物特异性代谢及隔离

Hepatic CYP1A induction by dioxin-like compounds, and congener-specific metabolism and sequestration in wild common cormorants from Lake Biwa, Japan.

作者信息

Kubota Akira, Iwata Hisato, Tanabe Shinsuke, Yoneda Kumiko, Tobata Sachiko

机构信息

Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.

出版信息

Environ Sci Technol. 2005 May 15;39(10):3611-9. doi: 10.1021/es048771g.

Abstract

The present study examines the effects of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) on hepatic cytochromes P450 (CYP) in the wild population of common cormorants from Lake Biwa, Japan, and discusses functional roles of CYP1A in terms of correlation analysis between tissue concentrations of individual congeners and expression levels of CYP1A. Levels of alkoxyresorufin (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase activities and a protein cross-reacted with anti-rat CYP1A1 polyclonal antibodies showed significant positive correlations with total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) or TEQs for most individual congeners in the liver of cormorants, suggesting induction of CYP1A-like protein by these chemicals. In contrast, TEQs for lower chlorinated congeners, 2,3,7,8-T4CDF and PCB77, showed relatively low correlations with the expression level of CYP1A-like protein. Concentrations of 2,3,7,8-T4CDF and PCB77 normalized to a relatively recalcitrant congener, PCB169, were negatively correlated with the CYP1A-like protein level. These results indicate preferential metabolism of those congeners by CYP1A-like protein that was induced by TEQs. Concentration ratios of liverto pectoral muscle for certain congeners significantly increased with an elevation of the CYP1A-like protein level. Comparing the results in the present study with those of previous studies using rodents treated with certain dioxin-like congeners, these congeners in the liver may be sequestered by CYP1A. Levels of cross-reactive proteins with anti-rat CYP2B1, CYP2C6, and CYP3A2 polyclonal antibodies correlated with neither TEQs nor liver/muscle concentration ratios of congeners. We conclude that the potential for CYP1A induction, and metabolism and sequestration of dioxin-like compounds by CYP1A, may be a critical factor for assessing the ecological risk in wild avian species.

摘要

本研究考察了多氯二苯并 - 对二噁英(PCDDs)、多氯二苯并呋喃(PCDFs)和共平面多氯联苯(Co - PCBs)对日本琵琶湖野生鸬鹚肝脏细胞色素P450(CYP)的影响,并通过个体同系物组织浓度与CYP1A表达水平之间的相关性分析,探讨了CYP1A的功能作用。烷氧基试卤灵(甲氧基 - 、乙氧基 - 、戊氧基 - 和苄氧基试卤灵)O - 脱烷基酶活性水平以及与抗大鼠CYP1A1多克隆抗体发生交叉反应的一种蛋白质,与鸬鹚肝脏中总的2,3,7,8 - 四氯二苯并 - 对二噁英毒性当量(TEQs)或大多数个体同系物的TEQs呈显著正相关,表明这些化学物质可诱导CYP1A样蛋白。相比之下,低氯同系物2,3,7,8 - T4CDF和PCB77的TEQs与CYP1A样蛋白的表达水平相关性相对较低。以相对难降解的同系物PCB169进行标准化后的2,3,7,8 - T4CDF和PCB77浓度,与CYP1A样蛋白水平呈负相关。这些结果表明,CYP1A样蛋白优先代谢由TEQs诱导产生的那些同系物。某些同系物的肝脏与胸肌浓度比随着CYP1A样蛋白水平的升高而显著增加。将本研究结果与先前使用某些二噁英类同系物处理过的啮齿动物的研究结果进行比较,肝脏中的这些同系物可能被CYP1A隔离。与抗大鼠CYP2B1、CYP2C6和CYP3A2多克隆抗体发生交叉反应的蛋白水平,与TEQs以及同系物的肝脏/肌肉浓度比均无相关性。我们得出结论,CYP1A的诱导潜力以及CYP1A对二噁英类化合物的代谢和隔离作用,可能是评估野生鸟类物种生态风险的关键因素。

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