Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers

Koh, Wen Xin; Hornbuckle, Keri C.; Kai, Wang; Thorne, Peter S.

doi:10.1016/j.envint.2016.06.014

Cited by 25 publications

(33 citation statements)

References 59 publications

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“…The numbers agree well with previously observed detection frequencies (~40%) of parent PCB 11 in AESOP study serum samples (Koh et al 2015). PCB sulfate levels were not found to be correlated between mothers and daughters or geographic origin, a finding that agrees well with previous quantitative analyses for OH-PCBs and parent PCB congeners (Marek et al 2014), even though more recent evidence reports moderate correlation of detectable PCB and OH-PCB serum levels and community of residence (Koh et al 2016b). …”

Section: Discussionsupporting

confidence: 89%

“…AESOP Study participants have mean (std dev) Σ 209 PCB levels of 0.5050 (0.5164) ng/g f.w. (Koh et al 2016b) and Σ 64 OH-PCB levels of 0.0637 (0.0463) ng/g f.w. (Koh et al 2016a).…”

Section: Discussionmentioning

confidence: 99%

“…Blood collection and serum preparation strictly occurred after informed consent of all study participants (Ampleman et al 2015; Koh et al 2015; Koh et al 2016b; Marek et al 2013; Marek et al 2014). …”

Section: Methodsmentioning

confidence: 99%

“…To test this hypothesis, we initially evaluated the acid stability and solvent extraction efficiency of sulfate metabolites of OH-PCBs, and demonstrate that while they appear to be stable, they would not be co-extracted, and thus effectively neglected, in conventional methods for PCB and OH-PCB analysis in biological samples. As a feasible alternative we applied an LC-MSMS (UPLC/TQD) approach to quantify dichlorinated PCB sulfates in human serum samples obtained from 46 PCB exposed individuals (Ampleman et al 2015; Koh et al 2015; Koh et al. 2016b; Marek et al 2013; Marek et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a sulfate metabolite of PCB 11 in human serum

Grimm

Lehmler

Koh

et al. 2017

Environment International

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Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20 % of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past.

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Section: Discussionsupporting

confidence: 89%

“…AESOP Study participants have mean (std dev) Σ 209 PCB levels of 0.5050 (0.5164) ng/g f.w. (Koh et al 2016b) and Σ 64 OH-PCB levels of 0.0637 (0.0463) ng/g f.w. (Koh et al 2016a).…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a sulfate metabolite of PCB 11 in human serum

Grimm

Lehmler

Koh

et al. 2017

Environment International

Self Cite

View full text Add to dashboard Cite

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“…1–10 Despite restrictions and banning in most parts of the world through the Stockholm Convention on Persistent Organic Pollutants (POPs), levels of well-studied “legacy” compounds, including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are routinely detected in human and wildlife tissues where they continue to pose significant health risks to highly exposed and susceptible populations. 11–17 In addition to anthropogenic sources, more than 4,500 HOCs are synthesized by microbes and algae, 1,18 and many of these natural products strongly resemble banned anthropogenic chemicals or their metabolites.…”

Section: Introductionmentioning

confidence: 99%

Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca²⁺ Dynamics

Zheng

McKinnie

Gamal

et al. 2018

Environ. Sci. Technol.

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Contemporary sources of organohalogens produced as disinfection byproducts (DBPs) are receiving considerable attention as emerging pollutants because of their abundance, persistence, and potential to structurally mimic natural organohalogens produced by bacteria that serve signaling or toxicological functions in marine environments. Here, we tested 34 organohalogens from anthropogenic and marine sources to identify compounds active toward ryanodine receptor (RyR1), known toxicological targets of non-dioxinlike polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). [3H]Ryanodine ([3H]Ry) binding screening (≤2 μM) identified 10 highly active organohalogens. Further analysis indicated that 2,3-dibromoindole (14), tetrabromopyrrole (31), and 2,3,5-tribromopyrrole (34) at 10 μM were the most efficacious at enhancing [3H]Ry binding. Interestingly, these congeners also inhibited microsomal sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ ATPase (SERCA1a). Dual SERCA1a inhibition and RyR1 activation triggered Ca2+ efflux from microsomal vesicles with initial rates rank ordered 31 > 34 > 14. Hexabromobipyrroles (25) enhanced [3H]Ry binding moderately with strong SERCA1a inhibition, whereas pyrrole (24), 2,3,4-tribromopyrrole (26), and ethyl-4-bromopyrrole-2-carboxylate (27) were inactive. Of three PBDE derivatives of marine origin active in the [3H]Ry assay, 4′-hydroxy-2,3′,4,5′,6-pentabromodiphenyl ether (18) was also a highly potent SERCA1a inhibitor. Molecular targets of marine organohalogens that are also DBPs of emerging environmental concern are likely to contribute to their toxicity.

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PCB 95 promotes dendritic growth in primary rat hippocampal neurons via mTOR-dependent mechanisms

et al. 2018

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Polychlorinated biphenyls (PCBs), and in particular non-dioxin-like (NDL) congeners, continue to pose a significant risk to the developing nervous system. PCB 95, a prevalent NDL congener in the human chemosphere, promotes dendritic growth in rodent primary neurons by activating calcium-dependent transcriptional mechanisms that normally function to link activity to dendritic growth. Activity-dependent dendritic growth is also mediated by calcium-dependent translational mechanisms involving mechanistic target of rapamycin (mTOR), suggesting that the dendrite-promoting activity of PCB 95 may also involve mTOR signaling. Here, we test this hypothesis using primary neuron-glia co-cultures derived from the hippocampi of postnatal day 0 Sprague Dawley rats. PCB 95 (1 nM) activated mTOR in hippocampal cultures as evidenced by increased phosphorylation of mTOR at ser2448. Pharmacologic inhibition of mTOR signaling using rapamycin (20 nM), FK506 (5 nM), or 4EGI-1 (1 µM), and siRNA knockdown of mTOR, or the mTOR complex binding proteins, raptor or rictor, blocked PCB 95-induced dendritic growth. These data identify mTOR activation as a novel molecular mechanism contributing to the effects of PCB 95 on dendritic arborization. In light of clinical data linking gain-of-function mutations in mTOR signaling to neurodevelopmental disorders, our findings suggest that mTOR signaling may represent a convergence point for gene by environment interactions that confer risk for adverse neurodevelopmental outcomes.

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Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers

Cited by 25 publications

References 59 publications

Identification of a sulfate metabolite of PCB 11 in human serum

Identification of a sulfate metabolite of PCB 11 in human serum

Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca²⁺ Dynamics

PCB 95 promotes dendritic growth in primary rat hippocampal neurons via mTOR-dependent mechanisms

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Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers

Cited by 25 publications

References 59 publications

Identification of a sulfate metabolite of PCB 11 in human serum

Identification of a sulfate metabolite of PCB 11 in human serum

Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca2+ Dynamics

PCB 95 promotes dendritic growth in primary rat hippocampal neurons via mTOR-dependent mechanisms

Contact Info

Product

Resources

About

Organohalogens Naturally Biosynthesized in Marine Environments and Produced as Disinfection Byproducts Alter Sarco/Endoplasmic Reticulum Ca²⁺ Dynamics