Takeuchi Shinji, Anezaki Katsunori, Kojima Hiroyuki
Hokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan.
Hokkaido Research Organization, Environmental and Geological Research Department, Institute of Environmental Sciences, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan.
Environ Pollut. 2017 Aug;227:306-313. doi: 10.1016/j.envpol.2017.04.059. Epub 2017 May 10.
In recent years, some pigments and chemical products have been reported to contain polychlorinated biphenyl (PCB) congeners as unintentional byproducts, and these have also been detected in residential environments from indoor air and house dust. In this study, using in vitro reporter gene assays, we characterized the agonistic and antagonistic activities of a total of 25 PCB congeners contained in pigments (PCB-1 to -16, -20, -35, -40, -52, -56, -77, -101, -126, and -153) against five nuclear hormone receptors, (estrogen receptor (ER) α/β, glucocorticoid receptor (GR), androgen receptor (AR), thyroid hormone receptor (TR) α1) and aryl hydrocarbon receptor (AhR). In the ERα/β assays, 19 and 13 of the 25 PCBs tested showed ERα/β agonistic and/or antagonistic activities, respectively. Relatively potent agonistic activities against ERα/β were found in PCB congeners possessing chlorides at positions 2 and 3. In the GR and AR assays, five and all of the 25 PCB congeners showed antagonistic activity, respectively. Among the anti-androgenic PCB congeners, the activities were more potent in PCB congeners possessing more than three chlorides including consecutive ortho- and meta- or meta- and para-chlorides. In the AhR assay using a sensitive DR-EcoScreen cell line, five of the 25 PCB congeners showed agonistic activity. We newly found that PCB-1, -35 and -56 can act as AhR agonists. Despite these activities among the PCBs, the effects of PCB-11, mainly detected in pigments and chemical products, against these receptors were found to be weaker than those of other tested PCBs. These results suggest that unintentional PCBs in pigments and chemical products might act as agonists and/or antagonists against ERα/β, AR, GR, and AhR, and some of the PCBs might disrupt endocrine functions via multiple receptors and/or simultaneously induce dioxin-like activity via AhR.
近年来，有报道称一些颜料和化学产品含有多氯联苯（PCB）同系物作为无意产生的副产物，并且在室内空气和室内灰尘等居住环境中也检测到了这些物质。在本研究中，我们使用体外报告基因分析方法，对颜料中含有的总共25种PCB同系物（PCB - 1至 - 16、 - 20、 - 35、 - 40、 - 52、 - 56、 - 77、 - 101、 - 126和 - 153）针对五种核激素受体（雌激素受体（ER）α/β、糖皮质激素受体（GR）、雄激素受体（AR）、甲状腺激素受体（TR）α1）和芳烃受体（AhR）的激动和拮抗活性进行了表征。在ERα/β分析中，所测试的25种PCB中有19种和13种分别显示出ERα/β激动和/或拮抗活性。在2位和3位含有氯原子的PCB同系物中发现了相对较强的针对ERα/β的激动活性。在GR和AR分析中，25种PCB同系物分别有5种和全部显示出拮抗活性。在抗雄激素的PCB同系物中，在含有三个以上氯原子（包括连续的邻位和间位或间位和对位氯原子）的PCB同系物中活性更强。在使用敏感的DR - EcoScreen细胞系的AhR分析中，25种PCB同系物中有5种显示出激动活性。我们新发现PCB - 1、 - 35和 - 56可作为AhR激动剂。尽管这些PCB具有这些活性，但主要在颜料和化学产品中检测到的PCB - 11对这些受体的作用被发现比其他测试的PCB弱。这些结果表明，颜料和化学产品中无意产生的PCB可能作为针对ERα/β、AR、GR和AhR的激动剂和/或拮抗剂，并且一些PCB可能通过多种受体破坏内分泌功能和/或同时通过AhR诱导二噁英样活性。
