Department of Public Health, Centre for Arctic Health & Cellular and Molecular Toxicology, Aarhus University, Aarhus, Denmark.
Basic Clin Pharmacol Toxicol. 2014 Jul;115(1):118-28. doi: 10.1111/bcpt.12263. Epub 2014 May 29.
Persistent organic pollutants (POPs) include lipophilic legacy POPs and the amphiphilic perfluorinated alkyl acids (PFAAs). They have long half-lives and bioaccumulate in the environment, animals and human beings. POPs possess toxic, carcinogenic and endocrine-disrupting potentials. Endocrine-disrupting chemicals (EDCs) are compounds that either mimic or block endogenous hormones and thus disrupt the normal hormone homeostasis. Biomonitoring assesses the internal doses of a person to provide information about chemical exposures. Effect biomarkers assess chemicals potential to affect cellular functions in vivo/ex vivo. Human beings are exposed to complex mixtures of chemicals, having individually very different biological potentials and effects. Therefore, the assessment of the combined, integrated biological effect of the actual chemical mixture in human blood is important. In vitro and ex vivo cell systems have been introduced for the assessment of the integrated level of xenobiotic cellular effects in human beings. Ex vivo studies have shown geographical differences in bioaccumulated POP serum levels, being reflected by the combined biomarker effects of the complex mixture extracted from human serum. Xenohormone receptor transactivities can be used as an ex vivo integrated biomarker of POP exposure and effects. Epidemiological and in vitro/ex vivo studies have supported the potential impact of the combined effect of serum POPs on the activity of hormone and/or dioxin receptors as a risk factor for human health. With focus on hormone disruption, this MiniReview will give an update on recent POP-related endocrine-disrupting effects in vitro/ex vivo/in vivo and some related genetic data.
持久性有机污染物(POPs)包括亲脂性的旧 POPs 和两亲性全氟烷基酸(PFAAs)。它们具有长半衰期,并在环境、动物和人类中生物累积。POPs 具有毒性、致癌性和内分泌干扰潜力。内分泌干扰化学物质(EDCs)是模拟或阻断内源性激素的化合物,从而扰乱正常的激素平衡。生物监测评估一个人的内部剂量,以提供有关化学暴露的信息。效应生物标志物评估化学物质在体内/体外影响细胞功能的潜力。人类暴露于复杂的化学物质混合物中,每种化学物质具有非常不同的生物学潜力和效应。因此,评估实际化学混合物在人类血液中的综合、综合生物学效应非常重要。体外和离体细胞系统已被引入用于评估人类细胞中外来化学物质的综合水平效应。离体研究表明,生物累积的 POP 血清水平存在地理差异,这反映在从人血清中提取的复杂混合物的综合生物标志物效应中。外源性激素受体转活性可作为 POP 暴露和效应的体外综合生物标志物。流行病学和体外/离体研究支持血清 POPs 联合作用对激素和/或二恶英受体活性的潜在影响,作为人类健康的一个风险因素。本文聚焦于激素干扰,综述了最近关于 POPs 的体外/离体/体内内分泌干扰效应及其相关遗传数据。