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壬基酚聚氧乙烯醚(NP-9)在秀丽隐杆线虫中的代际毒性。

Intergenerational toxicity of nonylphenol ethoxylate (NP-9) in Caenorhabditis elegans.

机构信息

Environmental and Computational Chemistry Group, University of Cartagena, Cartagena, Colombia.

School of Population Health & Environmental Sciences, Faculty of Life Science & Medicine, King's College London, London, UK.

出版信息

Ecotoxicol Environ Saf. 2020 Jul 1;197:110588. doi: 10.1016/j.ecoenv.2020.110588. Epub 2020 Apr 11.

Abstract

The ethoxylated isomers of nonylphenol (NPEs, NP-9) are one of the main active ingredients present in nonionic surfactants employed as herbicides, cosmetics, paints, plastics, disinfectants and detergents. These chemicals and their metabolites are commonly found in environmental matrices. The aim of this work was to evaluate the intergenerational toxicity of NP-9 in Caenorhabditis elegans. The lethality, length, width, locomotion and lifespan were investigated in the larval stage L4 of the wild strain N2. Transgenic green fluorescent protein (GFP) strains were employed to estimate changes in relative gene expression. RT-qPCR was utilized to measure mRNA expression for neurotoxicity-related genes (unc-30, unc-25, dop-3, dat-1, mgl-1, and eat-4). Data were obtained from parent worms (P0) and the first generation (F1). Lethality of the nematode was concentration-dependent, with 48 h-LC values of 3215 and 1983 μM in P0 and F1, respectively. Non-lethal concentrations of NP-9 reduced locomotion. Lifespan was also decreased by the xenobiotic, but the negative effect was greater in P0 than in F1. Non-monotonic concentration-response curves were observed for body length and width in both generations. The gene expression profile in P0 was different from that registered in F1, although the expression of sod-4, hsp-70, gpx-6 and mtl-2 increased with the surfactant concentration in both generations. None of the tested genes followed a classical concentration-neurotoxicity relationship. In P0, dopamine presented an inverted-U curve, while GABA and glutamate displayed a bimodal type. However, in F1, inverted U-shaped curves were revealed for these genes. In summary, NP-9 induced intergenerational responses in C. elegans through mechanisms involving ROS, and alterations of the GABA, glutamate, and dopamine pathways.

摘要

壬基酚乙氧基化物(NPEs,NP-9)是作为除草剂、化妆品、油漆、塑料、消毒剂和洗涤剂中使用的非离子表面活性剂的主要活性成分之一。这些化学物质及其代谢物通常存在于环境基质中。本工作旨在评估 NP-9 在秀丽隐杆线虫中的代际毒性。在野生型 N2 的幼虫 L4 阶段,研究了 NP-9 的致死率、体长、体宽、运动和寿命。使用转绿色荧光蛋白(GFP)的转基因株系来估计相对基因表达的变化。通过 RT-qPCR 测量神经毒性相关基因(unc-30、unc-25、dop-3、dat-1、mgl-1 和 eat-4)的 mRNA 表达。数据来自亲代线虫(P0)和第一代(F1)。线虫的致死率与浓度呈依赖性,P0 和 F1 的 48 h-LC50 值分别为 3215 和 1983 μM。非致死浓度的 NP-9 降低了运动能力。寿命也因该外来化合物而缩短,但 P0 的负面影响大于 F1。在两代中,体长和体宽均观察到非单调浓度-反应曲线。P0 的基因表达谱与 F1 不同,尽管 sod-4、hsp-70、gpx-6 和 mtl-2 的表达在两代中均随表面活性剂浓度的增加而增加。所测试的基因均未遵循经典的浓度-神经毒性关系。在 P0 中,多巴胺呈倒 U 型曲线,而 GABA 和谷氨酸呈双峰型。然而,在 F1 中,这些基因呈现出倒 U 型曲线。总之,NP-9 通过涉及 ROS 的机制在 C. elegans 中诱导了代际反应,并改变了 GABA、谷氨酸和多巴胺途径。

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