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在家鸡(原鸡)胚胎中全氟辛烷磺酸(PFOS)的毒性,且对过氧化物酶体增殖物激活受体α(PPARα)调控的基因无影响。

Perfluorooctane sulfonate (PFOS) toxicity in domestic chicken (Gallus gallus domesticus) embryos in the absence of effects on peroxisome proliferator activated receptor alpha (PPARalpha)-regulated genes.

作者信息

O'Brien Jason M, Carew Amanda C, Chu Shaogang, Letcher Robert J, Kennedy Sean W

机构信息

Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2009 May;149(4):524-30. doi: 10.1016/j.cbpc.2008.11.009. Epub 2008 Dec 6.

Abstract

Perfluorooctane sulfonate (PFOS) is a widely distributed industrial compound that has been detected in the eggs of various wild avian species. Laboratory studies have indicated that PFOS is embryotoxic to domestic chickens (Gallus gallus domesticus), but the mechanisms of toxicity in the developing avian embryo remain unknown. We recently demonstrated that PFOS acts as a peroxisome proliferator by causing increased expression of peroxisome proliferator activated receptor alpha (PPARalpha)-regulated genes in cultured primary chicken embryo hepatocytes. The present study examined whether PPARalpha-regulated genes were dose-dependently affected in chicken embryos exposed in ovo to PFOS. White leghorn chicken eggs were injected with 0.1, 5.0 or 100.0 microg PFOS/g egg into the air cell prior to incubation. Embryos were incubated until pipping, after which the expression of PPARalpha-regulated genes was measured in the liver tissue of surviving embryos using real-time reverse transcription polymerase chain reaction. A dose-dependent decrease in embryo pippability was observed with an LD50 of 93 microg/g (3.54 microg/g-672,910 microg/g, 95% confidence interval). Hepatic PFOS concentrations increased concomitantly with dose. The PPARalpha-regulated genes measured were peroxisomal acyl CoA oxidase, bifunctional enzyme, liver fatty acid binding protein and peroxisomal 3-ketoacyl thiolase. PFOS exposure via egg injection prior to incubation did not affect the transcriptional activity of any of the assayed PPARalpha-regulated genes at any of the doses examined in day 21 chicken embryos.

摘要

全氟辛烷磺酸(PFOS)是一种广泛分布的工业化合物,已在多种野生鸟类的蛋中被检测到。实验室研究表明,PFOS对家鸡(Gallus gallus domesticus)具有胚胎毒性,但在发育中的鸟类胚胎中的毒性机制仍不清楚。我们最近证明,PFOS通过在培养的原代鸡胚肝细胞中引起过氧化物酶体增殖物激活受体α(PPARα)调节基因的表达增加,从而作为一种过氧化物酶体增殖剂发挥作用。本研究检测了在卵内暴露于PFOS的鸡胚中,PPARα调节基因是否受到剂量依赖性影响。在孵化前,将0.1、5.0或100.0微克PFOS/克蛋注射到白来航鸡的气室中。胚胎孵化至啄壳,之后使用实时逆转录聚合酶链反应在存活胚胎的肝脏组织中测量PPARα调节基因的表达。观察到胚胎啄壳能力呈剂量依赖性下降,半数致死剂量为93微克/克(3.54微克/克 - 672,910微克/克,95%置信区间)。肝脏中的PFOS浓度随剂量增加而升高。所检测的PPARα调节基因包括过氧化物酶体酰基辅酶A氧化酶、双功能酶、肝脏脂肪酸结合蛋白和过氧化物酶体3 - 酮酰基硫解酶。在孵化前通过蛋注射暴露于PFOS,在第21天的鸡胚中,在所检测的任何剂量下,均未影响所测定的任何PPARα调节基因的转录活性。

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