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四溴双酚 A 暴露对土壤线虫秀丽隐杆线虫的毒理学评估及作用机制。

Toxicological assessment and underlying mechanisms of tetrabromobisphenol A exposure on the soil nematode Caenorhabditis elegans.

机构信息

State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Branch of Shanghai, Yonker Environmental Protection Co., Ltd, Shanghai, 200051, China.

出版信息

Chemosphere. 2020 Mar;242:125078. doi: 10.1016/j.chemosphere.2019.125078. Epub 2019 Oct 8.

DOI:10.1016/j.chemosphere.2019.125078
PMID:31704520
Abstract

The widespread use of tetrabromobisphenol A (TBBPA) in industries has resulted in its frequent detection in environmental matrices, and the mechanisms of its associated hazards need further investigation. In this study, the nematode Caenorhabditis elegans (C. elegans) was exposed to environmentally relevant concentrations of TBBPA (0, 0.1, 1, 10, 100, 200 μg/L) to determine its effects. At TBBPA concentrations above 1 μg/L, the number of head thrashes, as the most sensitive physiological indicator, decreased significantly. Using the Illumina HiSeq™ 2000 sequencer, differentially expressed genes (DEGs) were determined, and 52 were down regulated and 105 were up regulated in the 200 μg/L TBBPA treatment group versus the control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database analysis demonstrated that dorso-ventral axis formation is related to neurotoxicity; metabolism of xenobiotics by Cytochrome P450 (CYP450) and glutathione-S-transferase (GST) was found to be the vital metabolic mechanisms and were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). GST was ascribed to the augmentation because mutations in cyp-13A7 were constrained under TBBPA exposure. Additionally, oxidative stress indicators accumulated in a dose-dependent relationship. These results will help understand the molecular basis for TBBPA-induced toxicity in C. elegans and open novel avenues for facilitating the exploration of more efficient strategies against TBBPA toxicity.

摘要

四溴双酚 A(TBBPA)在工业中的广泛应用导致其在环境基质中频繁检出,其相关危害的机制需要进一步研究。在这项研究中,使用秀丽隐杆线虫(C. elegans)暴露于环境相关浓度的 TBBPA(0、0.1、1、10、100、200μg/L)来确定其影响。在 TBBPA 浓度高于 1μg/L 时,作为最敏感的生理指标的头部抽搐次数显著减少。使用 Illumina HiSeq™ 2000 测序仪,确定差异表达基因(DEGs),与对照组相比,在 200μg/L TBBPA 处理组中,有 52 个基因下调,105 个基因上调。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路数据库分析表明,背腹轴形成与神经毒性有关;细胞色素 P450(CYP450)和谷胱甘肽-S-转移酶(GST)代谢外源化合物被认为是重要的代谢机制,并通过定量实时聚合酶链反应(qRT-PCR)得到证实。GST 被归因于增强,因为在 TBBPA 暴露下,cyp-13A7 的突变受到限制。此外,氧化应激指标呈剂量依赖性积累。这些结果将有助于理解 TBBPA 诱导的 C. elegans 毒性的分子基础,并为探索更有效的 TBBPA 毒性应对策略开辟新途径。

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