Perfluoroalkyl acids (PFAAs) are detectable in human blood. PFAA exposure may contribute to androgen receptor (AR)-related health effects such as prostate cancer (PCa). In Norway and Sweden, exposures to PFAAs and PCa are very real concerns. In vitro studies conventionally do not investigate PFAA-induced AR disruption at human blood-based concentrations, thus limiting application to human health. We aim to determine the endocrine disrupting activity of PFAAs based upon human exposure levels, on AR transactivation and translocation. PFAAs (PFOS, PFOA, PFNA, PFDA, PFHxS, and PFUnDA) were tested at concentrations ranging from 1/10 × to 500 × relative to human blood based upon the exposure levels observed in a Scandinavian population. Translocation was measured by high content analysis (HCA) and transactivation was measured by reporter gene assay (RGA). No agonist activity (translocation or transactivation) was detected for any PFAAs. In the presence of testosterone, AR translocation increased following exposure to PFOS 1/10 × and 100 ×, PFOA 1/10 ×, and PFNA 1 × and 500 × (P < 0.05). In the presence of testosterone, PFOS 500 × antagonised AR transactivation, whereas PFDA 500 × increased AR transactivation (P < 0.05). PFAAs may contribute to AR-related adverse health effects such as PCa. PFAAs can disrupt AR signalling via two major components: translocation and transactivation. PFAAs which disrupt one signalling component do not necessarily disrupt both. Therefore, to fully investigate the disruptive effect of human exposure-based contaminants on AR signalling, it is imperative to analyse multiple molecular components as not all compounds induce a disruptive effect at the same level of receptor signalling.

中文翻译：

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人为基础的全氟烷基酸暴露水平可能会破坏雄激素受体信号转导的主要成分，从而对健康产生有害影响。

在人类血液中可检测到全氟烷基酸（PFAA）。PFAA暴露可能会导致雄激素受体（AR）相关的健康影响，例如前列腺癌（PCa）。在挪威和瑞典，对PFAA和PCa的暴露是非常现实的问题。体外研究通常不研究以人血为基础的浓度下PFAA诱导的AR破坏，因此限制了其对人类健康的应用。我们旨在确定基于人类暴露水平，AR反式激活和易位的PFAA的内分泌干扰活性。根据在斯堪的纳维亚人群中观察到的暴露水平，对PFAA（PFOS，PFOA，PFNA，PFDA，PFHxS和PFUnDA）的测试浓度相对于人血为1/10×至500×。通过高含量分析（HCA）测量易位，通过报告基因测定（RGA）测量反式激活。没有检测到任何PFAA的激动剂活性（易位或反式激活）。在存在睾酮的情况下，暴露于PFOS 1/10×和100×，PFOA 1/10×和PFNA 1×和500×后，AR转运增加（P <0.05）。在存在睾丸激素的情况下，PFOS 500×拮抗了AR的反式激活，而PFDA 500×增强了AR的反式激活（P <0.05）。PFAAs可能会导致与AR相关的不良健康影响，例如PCa。PFAA可以通过两个主要成分破坏AR信号传导：易位和反激活。破坏一个信号成分的PFAA不一定会破坏两者。因此，要全面研究基于人类暴露的污染物对AR信号的破坏作用，必须分析多种分子成分，因为并非所有化合物都在相同水平的受体信号下诱导破坏作用。