Hepatic CYP1A induction by dioxin-like compounds, and congener-specific metabolism and sequestration in wild common cormorants from Lake Biwa, Japan
Hepatic CYP1A induction by dioxin-like compounds, and congener-specific metabolism and sequestration in wild common cormorants from Lake Biwa, Japan
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DOI：
10.1021/es048771g
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发表时间：
2005-05-15
影响因子：
11.4
通讯作者：
Tobata, S
中科院分区：
文献类型：
--
作者：
Kubota, A;Iwata, H;Tobata, S
本研究探讨了多氯二苯并对二恶英（PCDDs），多氯二苯并呋喃（PCDFs），和共面多氯联苯（Co-PCBs）对肝脏细胞色素P450（CYP）的影响，在野生种群的共同鸬鹚从日本琵琶湖，并讨论了CYP 1A的功能作用的相关性分析的组织浓度的个别同源物和CYP 1A的表达水平。烷氧基试卤灵（甲氧基-，乙氧基-，戊氧基-和苄氧基试卤灵）O-脱烷基酶活性和蛋白质的水平与抗大鼠CYP 1A 1多克隆抗体交叉反应，显示出显着的正相关性与总2，3，7，8-四氯二苯并-p-二恶英毒性当量（TEQs）或TEQs的大多数个别同源物在鸬鹚的肝脏，这表明CYP 1A样蛋白的诱导这些化学品。相比之下，低氯化同系物，2，3，7，8-T4 CDF和PCB 77的毒性当量与CYP 1A样蛋白表达水平的相关性相对较低。2，3，7，8-T4 CDF和PCB 77的浓度标准化为一个相对较强的柠檬酸同系物，PCB 169，与CYP 1A样蛋白水平呈负相关。这些结果表明，这些同系物的优先代谢的CYP 1A样蛋白，诱导TEQs。某些同源物的肝脏胸肌的浓度比显着增加的CYP 1A样蛋白水平的升高。将本研究的结果与先前使用某些二恶英类同系物处理啮齿动物的研究结果进行比较，发现肝脏中的这些同系物可能被CYP 1A螯合。与抗大鼠CYP 2B 1、CYP 2C 6和CYP 3A 2多克隆抗体的交叉反应蛋白水平与同源物的TEQ和肝脏/肌肉浓度比均不相关。我们的结论是，潜在的CYP 1A诱导，代谢和螯合二恶英类化合物的CYP 1A，可能是一个关键因素，评估野生鸟类的生态风险。
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-tetra chlorodibenzo-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 liver to 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.