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商业环烷酸和油砂加工水中的有机部分对小鼠促炎基因表达和巨噬细胞吞噬作用的影响不同。

Commercial naphthenic acids and the organic fraction of oil sands process water induce different effects on pro-inflammatory gene expression and macrophage phagocytosis in mice.

机构信息

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2E9.

出版信息

J Appl Toxicol. 2012 Dec;32(12):968-79. doi: 10.1002/jat.1687. Epub 2011 May 24.

DOI:10.1002/jat.1687
PMID:21607992
Abstract

Naphthenic acids (NAs) are believed to be the major toxic component of oil sands process water (OSPW). Different OSPW preparations have distinct NA compositions, and additional organics, that differ from the commercial NAs (C-NAs) often used for toxicology studies. To evaluate whether C-NAs are an adequate model to study OSPW toxicity in complex organisms, we compared the effects of C-NAs and the extractable organic fraction of OSPW (OSPW-OF) on mice immune mechanisms. Mice were orally exposed to different C-NA doses, or OSPW-OF at the same NA dose, for up to 8 weeks, and the expression of pro-inflammatory genes in different organs was determined using quantitative PCR. C-NAs and OSPW-OF altered the expression of pro-inflammatory genes, inducing either expression down-regulation or up-regulation, depending on the organ examined and time after exposure. The time at which gene expression alterations occurred, and the specific sets of genes whose expression was altered, were very different between animals exposed to C-NAs or to OSPW-OF. We evaluated the ability of mouse peritoneal macrophages to phagocytose yeast cell wall, as a measure of the ability of mice to mount a central function of the innate immune response. Phagocytosis was significantly reduced in animals exposed to C-NAs, but enhanced in mice exposed to OSPW-OF. Our results indicate that studies using C-NAs may not necessarily reflect the possible effects induced in animals by process water from tailing ponds.

摘要

环烷酸(NA)被认为是油砂开采废水(OSPW)中的主要毒性成分。不同的 OSPW 制剂具有不同的 NA 组成,以及与常用于毒理学研究的商业 NA(C-NA)不同的其他有机物。为了评估 C-NA 是否是研究复杂生物中 OSPW 毒性的合适模型,我们比较了 C-NA 和 OSPW 可萃取有机物部分(OSPW-OF)对小鼠免疫机制的影响。将小鼠口服暴露于不同剂量的 C-NA 或相同 NA 剂量的 OSPW-OF 中,持续长达 8 周,并使用定量 PCR 测定不同器官中促炎基因的表达。C-NA 和 OSPW-OF 改变了促炎基因的表达,根据所检查的器官和暴露后时间的不同,诱导表达下调或上调。在接受 C-NA 或 OSPW-OF 暴露的动物中,基因表达改变发生的时间以及改变表达的特定基因集非常不同。我们评估了小鼠腹腔巨噬细胞吞噬酵母细胞壁的能力,作为衡量小鼠先天免疫反应中心功能的一种手段。在接受 C-NA 暴露的动物中,吞噬作用明显降低,但在接受 OSPW-OF 暴露的动物中增强。我们的结果表明,使用 C-NA 进行的研究不一定能反映出池塘尾矿中工艺水可能对动物产生的影响。

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