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苯并[a]芘和 2,3-苯并呋喃诱导斑马鱼胚胎中 AhR 调节反应的不同时间模式(Danio rerio)。

Benzo[a]pyrene and 2,3-benzofuran induce divergent temporal patterns of AhR-regulated responses in zebrafish embryos (Danio rerio).

机构信息

Department of Ecosystem Analysis, Institute for Environmental Research, ABBt - Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany.

Man-Technology-Environment Research Centre, School of Science and Technology, Örebro University, Fakultetsgatan 1, 701 82, Örebro, Sweden.

出版信息

Ecotoxicol Environ Saf. 2019 Nov 15;183:109505. doi: 10.1016/j.ecoenv.2019.109505. Epub 2019 Aug 5.

DOI:10.1016/j.ecoenv.2019.109505
PMID:31394372
Abstract

Biotests like the fish embryo toxicity test have become increasingly popular in risk assessment and evaluation of chemicals found in the environment. The large range of possible endpoints is a big advantage when researching on the mode of action of a certain substance. Here, we utilized the frequently used model organism zebrafish (Danio rerio) to examine regulative mechanisms in the pathway of the aryl-hydrocarbon receptor (AHR) in early development. We exposed embryos to representatives of two chemical classes known to elicit dioxin-like activity: benzo[a]pyrene for polycyclic aromatic hydrocarbons (PAHs) and 2,3-benzofuran for polar O-substituted heterocycles as a member of heterocyclic compounds in general (N-, S-, O-heterocycles; NSO-hets). We measured gene transcription of the induced P450 cytochromes (cyp1), their formation of protein and biotransformation activity throughout the whole embryonic development until 5 days after fertilization. The results show a very specific time course of transcription depending on the chemical properties (e.g. halogenation, planarity, K), the physical decay and the biodegradability of the tested compound. However, although this temporal pattern was not precisely transferable onto the protein level, significant regulation in enzymatic activity over time could be detected. We conclude, that a careful choice of time and end point as well as consideration of the chemical properties of a substance are fairly important when planning, conducting and especially evaluating biotests.

摘要

生物测试,如鱼类胚胎毒性测试,在环境中化学物质的风险评估和评价中变得越来越流行。在研究某种物质的作用模式时,可能的终点范围很广,这是一个很大的优势。在这里,我们利用常用的模式生物斑马鱼(Danio rerio)来研究早期发育中芳香烃受体(AHR)途径中的调节机制。我们将胚胎暴露于两种已知具有二恶英样活性的化学物质代表物中:多环芳烃(PAHs)中的苯并[a]芘和杂环化合物中的极性 O-取代杂环的 2,3-苯并呋喃(作为杂环化合物的一般成员,N-、S-、O-杂环;NSO-het)。我们测量了整个胚胎发育过程中诱导的 P450 细胞色素(cyp1)的基因转录,以及它们的蛋白质形成和生物转化活性,直到受精后 5 天。结果表明,转录具有非常特定的时间过程,这取决于化学性质(例如卤化、平面性、K)、测试化合物的物理衰减和生物降解性。然而,尽管这种时间模式在蛋白质水平上不能精确地转移,但可以检测到酶活性随时间的显著调节。我们得出结论,在计划、进行特别是评估生物测试时,仔细选择时间和终点以及考虑物质的化学性质是非常重要的。

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