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首页> 外文期刊>Environmental toxicology and chemistry >Interindividual Variation in the Cytochrome P4501A Response to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Herring Gull Embryo Hepatocytes
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Interindividual Variation in the Cytochrome P4501A Response to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Herring Gull Embryo Hepatocytes

机译:细胞色素P4501A对2,3,7,8-四氯二苯甲苯苯并二恶英在鲱鱼鸥胚胎肝细胞的反应中的细胞

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Exposure to dioxin-like compounds is consistently associated with concentration-dependent induction of cytochrome P4501A (CYP1A) enzymes in primary cultures of avian hepatocytes. We have previously demonstrated that the median effective concentration (EC50) for induction of this response is predictive of in vivo sensitivity to dioxin-like compounds in birds. We investigated sources of interindividual variation in the CYP1A response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in wild herring gulls and considered how this variation may complicate dioxin sensitivity estimates based on the CYP1A bioassay. Concentration-dependent effects of TCDD on CYP1A mRNA expression were characterized in 55 hepatocyte cultures prepared from individual herring gull embryos. A large degree of variability was observed among the hepatocyte culture preparations. For example, 1) basal CYP1A4 and CYP1A5 mRNA expression varied by 20- and 126-fold, respectively, among individuals, and 2) exposure to TCDD induced CYP1A4 mRNA expression by 57-fold in the most responsive sample but did not significantly induce CYP1A4 mRNA expression above baseline values in 42% of hepatocyte culture preparations. Environmental and genetic factors contributing to the observed variability are discussed. Despite the large amount of interindividual variation, we conclude that reproducible EC50-based estimates of species sensitivity can be obtained from the CYP1A cell culture bioassay when samples are collected from relatively uncontaminated colonies. Environ Toxicol Chem 2019;38:660-670. (c) 2019 SETAC
机译:暴露于二恶英样化合物与禽肝细胞的原代培养物中的细胞色素P4501A(CYP1A)酶的浓度依赖性诱导始终如一。我们之前已经证明,用于诱导这种反应的中值有效浓度(EC50)是对鸟类中二恶英的化合物的体内敏感性预测性。我们研究了CYP1A对野生鲱鱼中的2,3,7,8-四氯二氯胺-P-二恶英(TCDD)的关联变异的来源,并考虑了这种变化如何基于CYP1A生物测定的二恶英敏感性估算。 TCDD对CYP1A mRNA表达的浓度依赖性作用在55例由个体鲱鱼鸥胚胎制备的肝细胞培养物中表征。在肝细胞培养制剂中观察到大程度的变异性。例如,1)基础CYP1A4和CYP1A5 mRNA表达分别在最敏感的样品中暴露于TCDD诱导的CYP1A4 mRNA表达57倍,但未显着诱导CYP1A4在肝细胞培养制剂的42%的基线值以上mRNA表达。讨论了对观察到的变异性有贡献的环境和遗传因素。尽管具有大量的接合变异,我们得出结论,当从相对未受污染的菌落收集样品时,可以从CYP1A细胞培养生物测定获得可重复的EC50基于物种敏感性的估计。环境毒素化学2019; 38:660-670。 (c)2019 Setac

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