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全氟羧酸和磺酸在虹鳟鱼雌激素受体结合及肝切片卵黄蛋白原mRNA表达试验中的雌激素活性

Estrogenic Activity of Perfluoro Carboxylic and Sulfonic Acids in Rainbow Trout Estrogen Receptor Binding and Liver Slice Vtg mRNA Expression Assays.

作者信息

Tapper Mark A, Denny Jeffrey S, Sheedy Barbara R, Johnson Ben, Kolanczyk Richard C

机构信息

USEPA, ORD, CCTE, GLTED, 6201 Congdon Boulevard, Duluth, MN 55804.

Wisconsin Veterinary Diagnostic Laboratory, 445 Easterday Ln. Madison, WI 53706.

出版信息

Appl In Vitro Toxicol. 2023 Mar 17;9(1):13-22. doi: 10.1089/aivt.2022.0013.

Abstract

Perfluoroalkylated substances (PFAS) such as carboxylic acids, and sulfonic acids were manufactured in high quantities and are ubiquitous environmental contaminants. These chemicals persist in the environment and tend to bioaccumulate. In the current study, the estrogenic potential of a series of perfluoro carboxylic acids and select perfluoro sulfonic acids were assessed in an rainbow trout estrogen receptor (rtER) binding assay and an rtER dependent vitellogenin (Vtg) expression rainbow trout liver slice assay. Perfluoro carboxylic acids with perfluoroalkyl chain lengths of four to six did not significantly bind to the rtER or induce Vtg expression in liver slices. Perfluoro carboxylic acids with chain lengths of seven to ten, and sulfonic acids with seven and eight carbon chains bound to the rtER, but with low relative binding affinities. While affinity for the rtER increased with increasing chain length the highest affinity measured was only 0.0025% relative to the endogenous hormone 17ß-estradiol at 100%. Both the eight-carbon carboxylic acid and eight-carbon sulfonic acid induced Vtg expression in ex vivo liver slices. However, toxicity did not allow expression to achieve maximum efficacy relative to estradiol.

摘要

全氟烷基化物质(PFAS),如羧酸和磺酸,曾被大量生产,是普遍存在的环境污染物。这些化学物质在环境中持久存在并易于生物累积。在本研究中,通过虹鳟鱼雌激素受体(rtER)结合试验和rtER依赖的卵黄蛋白原(Vtg)表达虹鳟鱼肝切片试验,评估了一系列全氟羧酸和选定的全氟磺酸的雌激素潜力。全氟烷基链长度为四至六个碳的全氟羧酸与rtER的结合不显著,也未在肝切片中诱导Vtg表达。链长度为七至十个碳的全氟羧酸以及碳链长度为七个和八个碳的磺酸与rtER结合,但相对结合亲和力较低。虽然对rtER的亲和力随链长度增加而增加,但测得的最高亲和力相对于内源性激素17β-雌二醇(100%时)仅为0.0025%。含八个碳的羧酸和含八个碳的磺酸均在离体肝切片中诱导了Vtg表达。然而,毒性使得表达相对于雌二醇无法达到最大效力。

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