毒理性
作为强烈的催泪剂，最可能的蛋白质靶标之一是TRPA1离子通道，它表达在眼睛、鼻子、嘴巴和肺部的感官神经（三叉神经）中。卤化的二苯并呋喃（多氯二苯并呋喃和polybrominated二苯并呋喃）结合芳烃受体（AhR），这增加了它在XRE（异生物质响应元件）启动子区域激活转录的能力。特别是AhR与PCDF结合，将其转移到细胞核中，并与芳烃核转运蛋白（ARNT）和异生物质响应元件（XRE）一起增加了CYP1A1和芳烃羟基酶（CYP1B1）的表达。AhR信号还通过环氧合酶-2增加花生四烯酸转化为前列腺素，改变Wnt/β-连环蛋白信号，下调Sox9，并改变炎症细胞因子受体的信号传导。AhR信号还改变类固醇激素受体的蛋白酶体降解，改变细胞的UVB应激反应，并改变某些T细胞亚群的分化。由此产生的AhR介导的激活和改变导致体重减轻、癌症和胸腺萎缩（免疫和内分泌紊乱的特征），这是对PCDFs和相关有毒卤化芳烃的常见毒性反应。
As a strong lachrymator, one of the most probable protein targets is the TRPA1 ion channel that is expressed in sensory nerves (trigeminal nerve) of the eyes, nose, mouth and lungs. Halogenated dibenzofurans (PCDFs and PBDFs) bind the aryl hydrocarbon receptor (AhR), which increases its ability to activate transcription in the XRE (xenobiotic resoponse element) promoter region. Specifically AhR binds to the PCDF, translocates it to the nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1 and aryl hydrocarbon hydroxylase (CYP1B1). AhR signaling also increseases conversion of arachidonic acid to prostanoids via cyclooxygenase-2, alters Wnt/beta-catenin signaling downregulating Sox9 and alters signaling by receptors for inflammatory cytokines. AhR signalling also alters proteasomal degradation of steroid hormone receptors, alters cellular UVB stress response and changes the differentiation of certain T-cell subsets. The resulting AhR mediated activation and alteration leads to body weight loss, cancer and thymic atrophy (characteristic of immune and endocrine disruption) which are common toxic responses to PCDFs and related toxic halogenated aryl hydrocarbons.
来源:Toxin and Toxin Target Database (T3DB)
