Effects of unintentional PCBs in pigments and chemical products on transcriptional activity via aryl hydrocarbon and nuclear hormone receptors

摘要

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) alpha/beta, glucocorticoid receptor (GR), androgen receptor (AR), thyroid hormone receptor (TR) alpha 1) and aryl hydrocarbon receptor (AhR). In the ER alpha/beta assays, 19 and 13 of the 25 PCBs tested showed ER alpha/beta agonistic and/or antagonistic activities, respectively. Relatively potent agonistic activities against ER alpha/beta 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 ER alpha/beta, 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. (C) 2017 Elsevier Ltd. All rights reserved.