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在二恶英样多氯联苯污染地区饲养的奶牛循环淋巴细胞中芳烃受体靶基因的调节。

Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area.

机构信息

Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy.

出版信息

Sci Total Environ. 2013 Apr 15;450-451:7-12. doi: 10.1016/j.scitotenv.2013.01.095. Epub 2013 Feb 27.

Abstract

Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes.

摘要

动物产品(如鱼类、蛋类、奶类及其制品)是人类接触二恶英、呋喃和类二恶英多氯联苯的主要来源。这些高度有毒和持久性污染物的负面影响是通过激活芳香烃受体(AHR)介导的,该受体引发了几种基因的转录诱导,包括那些参与外来生物代谢的基因。我们之前已经证明了 AHR 信号通路在牛血液淋巴细胞的原代培养中存在并发挥作用。本研究的目的是通过实时 PCR 检测天然暴露于 DL 化合物的奶牛未培养细胞中选定靶基因(即 AHR、AHR 核转位蛋白(ARNT)、AHR 抑制剂、CYP1A1 和 CYP1B1)的表达和诱导性。该研究在两组动物中进行,这些动物在高度污染的地区饲养,其污染程度因牛奶总量 TEQ 值的不同而不同,还有一组动物在无工业污染的地区饲养作为对照组。牛淋巴细胞仅表达可检测水平的 AHR、ARNT 和 CYP1B1 基因;此外,只有 CYP1B1 的表达似乎与 TEQ 值相关,在污染最严重的组中更高,并随着动物的脱污染而降低。最后,暴露于污染物的奶牛的淋巴细胞在体外用特定的 AHR 配体处理后,CYP1A1 和 CYP1B1 的诱导能力均降低。总之,我们的结果表明,受 DL 化合物污染的奶牛可能会显示循环淋巴细胞中 AHR 靶基因表达的显著变化。

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