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生态毒理学作用方式的毒代动力学分析的短期测试。

Short-Term Test for Toxicogenomic Analysis of Ecotoxic Modes of Action in .

机构信息

Fraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Auf dem Aberg 1, Schmallenberg 57392, Germany.

Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, Giessen 35392, Germany.

出版信息

Environ Sci Technol. 2022 Aug 16;56(16):11504-11515. doi: 10.1021/acs.est.2c01777. Epub 2022 Aug 4.

Abstract

In the environmental risk assessment of substances, toxicity to aquatic plants is evaluated using, among other methods, the 7 day sp. growth inhibition test following the OECD TG 221. So far, the test is not applicable for short-term screening of toxicity, nor does it allow evaluation of toxic modes of action (MoA). The latter is also complicated by the lack of knowledge of gene functions in the test species. Using ecotoxicogenomics, we developed a time-shortened 3 day assay in which allows discrimination of ecotoxic MoA. By examining the changes in gene expression induced by low effect concentrations of the pharmaceutical atorvastatin and the herbicide bentazon at the transcriptome and proteome levels, we were able to identify candidate biomarkers for the respective MoA. We developed a homology-based functional annotation pipeline for the reference genome of, which allowed overrepresentation analysis of the gene ontologies affected by both test compounds. Genes affected by atorvastatin mainly influenced lipid synthesis and metabolism, whereas the bentazon-responsive genes were mainly involved in light response. Our approach is therefore less time-consuming but sensitive and allows assessment of MoA in . Using this shortened assay, investigation of expression changes of the identified candidate biomarkers may allow the development of MoA-specific screening approaches in the future.

摘要

在物质的环境风险评估中,水生植物毒性可通过 OECD TG 221 规定的为期 7 天的 sp.生长抑制测试等方法进行评估。到目前为止,该测试不适用于短期毒性筛选,也无法评估毒性作用模式 (MoA)。这也因测试物种中基因功能的知识缺乏而变得复杂。通过生态毒理学基因组学,我们开发了一种缩短至 3 天的试验,该试验可区分生态毒性 MoA。通过在转录组和蛋白质组水平上检查低浓度的药物阿托伐他汀和除草剂苯达松对基因表达的诱导变化,我们能够确定各自 MoA 的候选生物标志物。我们为参考基因组开发了一个基于同源性的功能注释管道,该管道允许对受两种测试化合物影响的基因本体进行过表达分析。受阿托伐他汀影响的基因主要影响脂质合成和代谢,而苯达松响应的基因主要参与光反应。因此,我们的方法虽然耗时更短,但却更灵敏,并允许评估的作用模式。使用这种缩短的试验,对鉴定出的候选生物标志物表达变化的研究可能会在未来开发出特定作用模式的筛选方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c32f/9386900/f9b5453cff01/es2c01777_0002.jpg

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