T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs)

Schriks, Merijn; Vrabie, Cozmina M.; Gutleb, Arno C.; Faassen, Elisabeth J.; Rietjens, Ivonne M. C. M.; Murk, Albertinka J.

doi:10.1016/j.tiv.2005.09.001

Cited by 80 publications

(52 citation statements)

References 32 publications

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“…These results confirm those of our previous study using other PHAHs that PCBs, PBBs and PBDEs are not agonists for the TRβ, but instead acted as antagonists at very low concentration (RIC20s <5×10 -7 g/L) [21]. Similar results were reported by Schriks et al [7] for other PHAHs, where it was found that BDE206 was an antagonist and did not respond in the T-screen when tested in the absence of T 3 . PCNs were weaker TR antagonists than PCBs, PBBs and PBDEs, but had a similar antagonist activity as phenols, phthalate, pesticides and bisphenol A derivatives [21].…”

Section: Discussionsupporting

confidence: 92%

“…In particular, the polyhalogenated aromatic hydrocarbons (PHAHs), such as PCBs, PBDEs and PBBs, have attracted much attention because of their ability to disrupt thyroid function due to their environmental persistence and lipophilicity. For example, PCBs can decrease the levels of circulating thyroid hormones [6] and BDE209 was found to disrupt thyroid receptors (TRs) in vitro using the T-Screen method [7]. Meanwhile, in rodent studies, PBDEs reduced the circulating levels of thyroid hormones and showed an even closer structural relationship to 3,3′,5,5′-tetraiodo-L-thyronine (T 4 ) than PCBs [8].…”

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confidence: 99%

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In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures

Wang

et al. 2011

Chin. Sci. Bull.

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Polychlorinated naphthalenes (PCNs) are dioxin-like environmental contaminants. There is growing concern over the endocrine-disrupting effects of PCNs, but very few studies have investigated the effect of PCNs on the thyroid system. This study used a yeast two-hybrid assay, which included the recombinant human thyroid receptor(TR)-β and reporter genes, to characterize the TRβ-disrupting effects of five individual PCN congeners, five PCN Halowax mixtures, and naphthalene. Their agonist and antagonist effects were studied in the absence and presence of 5×10 -7 mol/L 3,3′,5-triiodo-L-thyronine, which induced submaximal β-galactosidase activity. Naphthalene, 1,2,3,4,5,6,7,8-octachloronaphthalene and all of the Halowax mixtures (Halowax 1000, 1001, 1013, 1014 and 1099) showed no agonist or antagonist activity on TRβ at the concentrations tested (up to 10 -2 g/L). The lighter PCN congeners, namely 1-chloronaphthalene, 2-chloronaphthalene, 1,4-dichloronaphthalene and 1,2,3,4-tetrachloronaphthalene showed no agonist activity but showed significant antagonist activity on TRβ. The 20% relative inhibitory concentrations of these PCNs were less than 9.13 × 10 -3 g/L. Thus, bioaccumulation of these lighter PCN congeners may disrupt the thyroid hormone system and inhibit TR-mediated cellular responses. Studies in the future should investigate the possible associations between the presence PCNs and adverse health outcomes.in vitro bioassay, thyroid hormone receptors, polychlorinated naphthalenes, yeast two-hybrid assay Citation:Li N, Ma M, Wang Z J, et al. In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures

Wang

et al. 2011

Chin. Sci. Bull.

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“…S1). The results obtained with the MTT assay correspond to those obtained with the resazurin detection assay (Schriks et al 2006), with only a slight and insignificant shift in the median-effect concentration (EC 50 ) of T 3 from 2.0 × 10 −10 to 6.1 × 10 −10 mol/L (Fig. S1).…”

Section: Tr Ant/agonistic Activity Of Metallic Compounds In the T-screensupporting

confidence: 69%

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Liu

Ren

et al. 2016

Environ Sci Pollut Res

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In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl 2 , ZnCl 2 , HgCl 2 , CuSO 4 , MnSO 4 , and MgSO 4 ). The results reveal that none of the tested metallic compounds showed TRagonistic activity, whereas ZnCl 2 , HgCl 2 , and CdCl 2 demonstrated TR antagonism. For the yeast assay, the dose-response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl 2 , HgCl 2 , and CdCl 2 were 9.1 × 10 −5 , 3.2 × 10 −6 , and 1.2 × 10 −6 mol/L, respectively. The T-screen also supported the finding that ZnCl 2 , HgCl 2 , and CdCl 2 decreased the cell proliferation at concentrations ranging from 10 −6 to 10 −4 mol/ L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds.

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“…33 As for OH-PBDEs, three TH-like OH-PBDEs acted as TR agonists in both GH3 cell proliferation assays and reporter gene assays using GH3 cells. 12,31,34 Using the reporter gene assay in Chinese hamster ovary cells, four OH-PBDEs (4 0 -OH-BDE-17, 4-OH-BDE-42, 4 0 -OH-BDE-49, 4-OH-BDE-90) did not show any agonistic activity, but 4-OH-BDE-90 exhibited a weak antagonistic activity for both TR isoforms. 35 In contrast, all the tested 18 OH-PBDEs showed 33 It is obvious that the results summarized above are fairly inconsistent, and both agonistic and antagonistic activities have been reported even for the same PBDE or OH-PBDE.…”

Section: Thyroid Hormone Receptor Pathwaymentioning

confidence: 99%

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Ren

Guo

2013

Environ. Sci.: Processes Impacts

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Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame retardant additives in commercial products. Bio-monitoring data show that PBDE concentrations have increased rapidly in the bodies of wildlife and human over the last few decades. Based on the studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive ineffectiveness and even cancer. Unfortunately, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways. The general approach in the mechanistic investigation is to examine the in vitro direct binding of a PBDE with a receptor, the in vitro recruitment of a co-activator or co-repressor by the ligand-bound receptor, and the participation of the ligand in the receptor-mediated transcription pathways in cells. It is hoped that further studies in this area would provide more insights into the potential risks of PBDEs to human health. Environmental impactPBDEs are a class of chemicals used as ame retardant additives in a wide variety of industrial and commercial products. Rising levels of PBDEs have been detected in the human body. The toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neuro-developmental decits, reproductive ineffectiveness and even cancer. However, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways.

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T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs)

Cited by 80 publications

References 32 publications

In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures

In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

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