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Methylated Polycyclic Aromatic Hydrocarbons and/or Their Metabolites are Important Contributors to the Overall Estrogenic Activity of Polycyclic Aromatic Hydrocarbon-Contaminated Soils

机译:甲基化多环芳烃和/或其代谢物是多环芳烃污染土壤总体雌激素活性的重要贡献者

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In the present study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay. Relative potencies were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist vertical bar C vertical bar 182,780 (vertical bar C vertical bar) and the aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone. Luciferase induction and CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD) activity were measured to assess whether the estrogenic activity was elicited by the compound itself and/or by its metabolites. Relative potencies ranged between 10(-7) and 10(-4). The ability of ICI to decrease luciferase activity stimulated by all compounds indicated that the induction responses were ER-dependent. The aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone decreased luciferase induction and EROD activity by several compounds, including the methylated chrysenes, suggesting that metabolites of these chemicals contributed to ER activation. Several PACs, such as acridine and its derivatives, appear to directly activate the ER. Furthermore, extracts of soils from industrial areas were examined using this bioassay, and estrogenic activity was detected in all soil samples. Mass-balance analysis using a combination of relative potencies and chemical analysis of the samples suggested that polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, such as 1-and 3-methylchrysene, are important contributors to the overall estrogenic activity. However, these results revealed that a considerable proportion of the estrogenic activity in the soil remained unexplained, indicating the presence of other significant estrogenic compounds. (C) 2017 SETAC
机译:在本研究中,使用VM7Luc4E2反式激活法研究了42种多环芳香族化合物(PAC)的雌激素潜力。确定相对效价用于质量平衡分析。此外,还测试了化合物与雌激素受体(ER)拮抗剂C垂直竖条182,780(C垂直竖条)和芳烃受体拮抗剂/ CYP1A1抑制剂α-萘黄酮的组合。测量了萤光素酶的诱导作用和依赖CYP1A1的乙氧基间苯二酚-O-脱乙基酶(EROD)的活性,以评估雌激素活性是由化合物本身和/或其代谢产物引起的。相对效力介于10(-7)和10(-4)之间。 ICI降低所有化合物刺激的萤光素酶活性的能力表明诱导反应是ER依赖性的。芳基烃受体拮抗剂/ CYP1A1抑制剂α-萘黄酮降低了几种化合物(包括甲基化的chrysenes)的荧光素酶诱导和EROD活性,表明这些化学物质的代谢产物有助于ER活化。几种PAC,例如a啶及其衍生物,似乎可以直接激活ER。此外,使用该生物测定法检查了工业区土壤的提取物,并在所有土壤样品中检测到雌激素活性。使用相对效力和样品化学分析相结合的质量平衡分析表明,多环芳烃(PAH)和烷基化PAH(例如1和3-甲基丙烯)是总体雌激素活性的重要贡献者。但是,这些结果表明,土壤中相当大比例的雌激素活性仍无法解释,表明存在其他重要的雌激素化合物。 (C)2017年SETAC

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