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首页> 外文期刊>Environmental toxicology and chemistry >Performance of Three-Dimensional Rainbow Trout (Oncorhynchus mykiss) Hepatocyte Spheroids for Evaluating Biotransformation of Pyrene
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Performance of Three-Dimensional Rainbow Trout (Oncorhynchus mykiss) Hepatocyte Spheroids for Evaluating Biotransformation of Pyrene

机译：三维虹鳟（Oncorhynchus mykiss）肝细胞球体在评估Bio生物转化中的性能

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摘要

The aquatic bioconcentration of a chemical is typically determined using conventional fish tests. To foster the approach of alternatives to animal testing, a combination of computational models and in vitro substrate depletion bioassays (e.g., primary hepatocytes) can be used. One recently developed in vitro assay is the three-dimensional (3D) hepatic spheroid model from rainbow trout (Oncorhynchus mykiss). The aim of the present study was to evaluate the metabolic competence of the 3D spheroids from rainbow trout when exposed to pyrene, using 2 different sampling procedures (SP1 and SP2). The results were compared with previously published intrinsic clearance (CL) results from S9 fractions and primary hepatocyte assays. Extraction of pyrene using SP1 suggested that the spheroids had depleted 33% of the pyrene within 4 h of exposure, reducing to 91% after 30 h. However, when applying SP2 a substantial amount (36%) of the pyrene was bound to the exposure vial within 2 h, decreasing after 6 h of exposure. Formation of hydroxypyrene-glucuronide (OH-PYR-Glu) was obtained throughout the study, displaying the metabolic competence of the 3D spheroids. The 2 sampling procedures yielded different CLin vitro, where pyrene depletion using SP2 was very similar to published studies using primary hepatocytes. The 3D spheroids demonstrated reproducibile, log-linear biotransformation of pyrene and displayed formation of OH-PYR-Glu, indicating their metabolic competence for 30 h or more. Environ Toxicol Chem 2019;38:1738-1747. (c) 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
机译：化学品的水生生物浓度通常使用常规鱼类测试来确定。为了促进替代动物测试的方法，可以使用计算模型和体外底物耗竭生物测定法（例如原代肝细胞）的组合。一种最近开发的体外测定法是来自虹鳟鱼（Oncorhynchus mykiss）的三维（3D）肝球体模型。本研究的目的是使用2种不同的采样程序（SP1和SP2）来评估虹鳟暴露于when时3D球体的代谢能力。将结果与先前发布的S9馏分和原代肝细胞分析的固有清除率（CL）结果进行了比较。使用SP1提取pyr表明，在暴露4小时内，类球体已消耗了33％的,，在30小时后减少到91％。但是，在使用SP2时，大量的h（36％）会在2小时内与曝光瓶结合，在曝光6小时后会减少。在整个研究过程中均获得了羟基py-葡糖醛酸苷（OH-PYR-Glu）的形成，显示了3D球体的代谢能力。这两种采样程序在体外产生了不同的CL，其中使用SP2进行pyr消耗与使用原代肝细胞进行的已发表研究非常相似。 3D球体表现出re的可再现，对数线性生物转化，并显示出OH-PYR-Glu的形成，表明它们的代谢能力长达30小时或更长时间。 Environ Toxicol Chem 2019; 38：1738-1747。 （c）2019作者。 Wiley Periodicals，Inc.代表SETAC发布的《环境毒理学和化学》。

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