-
The Journal of Biological Chemistry 2021Polychlorinated bisphenols (PCBs) continue to contaminate food chains globally where they concentrate in tissues and disrupt the endocrine systems of species throughout...
Polychlorinated bisphenols (PCBs) continue to contaminate food chains globally where they concentrate in tissues and disrupt the endocrine systems of species throughout the ecosphere. Hydroxylated PCBs (OH-PCBs) are major PCB metabolites and high-affinity inhibitors of human estrogen sulfotransferase (SULT1E1), which sulfonates estrogens and thus prevents them from binding to and activating their receptors. OH-PCB inhibition of SULT1E1 is believed to contribute significantly to PCB-based endocrine disruption. Here, for the first time, the molecular basis of OH-PCB inhibition of SULT1E1 is revealed in a structure of SULT1E1 in complex with OH-PCB1 (4'-OH-2,6-dichlorobiphenol) and its substrates, estradiol (E2), and PAP (3'-phosphoadenosine-5-phosphosulfate). OH-PCB1 prevents catalysis by intercalating between E2 and catalytic residues and establishes a new E2-binding site whose E2 affinity and positioning are greater than and competitive with those of the reactive-binding pocket. Such complexes have not been observed previously and offer a novel template for the design of high-affinity inhibitors. Mutating residues in direct contact with OH-PCB weaken its affinity without compromising the enzyme's catalytic parameters. These OH-PCB resistant mutants were used in stable transfectant studies to demonstrate that OH-PCBs regulate estrogen receptors in cultured human cell lines by binding the OH-PCB binding pocket of SULT1E1.
Topics: Enzyme Inhibitors; Estrogens; Humans; Hydroxylation; Models, Molecular; Polychlorinated Biphenyls; Receptors, Estrogen; Sulfotransferases
PubMed: 33524392
DOI: 10.1016/j.jbc.2021.100353 -
Regulatory Toxicology and Pharmacology... Mar 2021Non-dioxin like polychlorinated biphenyls (NDL PCB) are recognized neurotoxicants with implications on altered neurodevelopment and neurodegeneration in exposed...
Non-dioxin like polychlorinated biphenyls (NDL PCB) are recognized neurotoxicants with implications on altered neurodevelopment and neurodegeneration in exposed organisms. NDL PCB neurotoxic relative potency schemes have been developed for a single mechanism, namely activity toward the ryanodine receptor (RyR), or combined mechanisms including, but not limited to, alterations of RyR and dopaminergic pathways. We compared the applicability of the two neurotoxic equivalency (NEQ) schemes and applied each scheme to PCB mixtures found in environmental and human serum samples. A multiple mechanistic NEQ predicts higher neurotoxic exposure concentrations as compared to a scheme based on the RyR alone. Predictions based on PCB ortho categorization, versus homologue categorization, lead to a higher prediction of neurotoxic exposure concentrations, especially for the mMOA. The application of the NEQ schemes to PCB concentration data suggests that PCBs found in fish from US lakes represent a considerable NEQ exposure to fish consuming individuals, that indoor air of schools contained high NEQ concentrations representing an exposure concern when inhaled by children, and that levels already detected in the serum of adults and children may contribute to neurotoxicity. With further validation and in vivo exposure data the NEQ scheme would help provide a more inclusive measure of risk presented by PCB mixtures.
Topics: Animals; Dioxins; Environmental Monitoring; Fishes; Humans; Neurotoxicity Syndromes; Polychlorinated Biphenyls; United States; United States Environmental Protection Agency; Water Pollutants, Chemical
PubMed: 33346014
DOI: 10.1016/j.yrtph.2020.104842 -
Environment International May 2015Whereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received...
BACKGROUND
Whereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received relatively little attention in environmental epidemiology.
OBJECTIVES
To evaluate prenatal and postnatal exposures to PCB-153, a proxy of total PCB exposure, and their relation to inattention and activity in 5-year-old Inuits from the Cord Blood Monitoring Program.
METHODS
Prenatal exposure to PCBs was informed by cord plasma PCB-153 levels. We used a validated pharmacokinetic model to estimate monthly infants' levels across the first year of life. Inattention and activity were assessed by coding of video recordings of children undergoing fine motor testing. We used multivariable linear regression to evaluate the association between prenatal and postnatal PCB-153 levels and inattention (n=97) and activity (n=98) at 5years of age.
RESULTS
Cord plasma PCB-153 was not associated with inattention and activity. Each interquartile range (IQR) increase in estimated infant PCB-153 levels at 2months was associated with a 1.02% increase in the duration of inattention (95% CI: 0.04, 2.00). Statistical adjustment for the duration of breastfeeding slightly increased regression coefficients for postnatal level estimates, some of which became statistically significant for inattention (months: 2-4) and activity (months: 2-5).
CONCLUSIONS
Our study adds to the growing evidence of postnatal windows of development during which children are more susceptible to neurotoxicants like PCBs.
Topics: Attention; Attention Deficit Disorder with Hyperactivity; Child, Preschool; Environmental Exposure; Environmental Pollutants; Female; Fetal Blood; Humans; Infant; Inuit; Male; Models, Theoretical; Neurotoxins; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Regression Analysis
PubMed: 25796081
DOI: 10.1016/j.envint.2015.02.004 -
Environmental Toxicology and Chemistry Aug 2021Polychlorinated biphenyl exposure-response relationships for ecologically relevant endpoints in fish vary greatly whether based on lowest-effect thresholds (Berninger...
Polychlorinated biphenyl exposure-response relationships for ecologically relevant endpoints in fish vary greatly whether based on lowest-effect thresholds (Berninger and Tillitt 2019) or all-response data (sensitivity analyses), which precludes use of a single fitted model per endpoint to predict risk or injury to mixed fish populations. PCB = polychlorinated biphenyl.
Topics: Animals; Fishes; Polychlorinated Biphenyls; Reproduction
PubMed: 34291842
DOI: 10.1002/etc.5071 -
Journal of Hazardous Materials Feb 2022Polychlorinated biphenyls (PCBs) were classified as group I carcinogenic to humans, as their toxicological mechanisms have been associated with cancer initiation and...
Polychlorinated biphenyls (PCBs) were classified as group I carcinogenic to humans, as their toxicological mechanisms have been associated with cancer initiation and promotion. However, whether PCBs have effects on cancer progression are still largely veiled. Here, we for the first time discovered that a PCB quinone-type metabolite, namely PCB29-pQ, exposure significantly promoted aerobic glycolysis, a hallmark property of metabolic reprogramming in cancer progression. PCB29-pQ exposure activated corresponding glucose transporter type 1 (GLUT1)/integrin β1/Src/focal adhesion kinase (FAK) signaling pathway in breast cancer MDA-MB-231 cells. Conversely, the inhibition of GLUT1 reversed this effect, as well as the ability of migration and invasion of MDA-MB-231 cells. In addition, PCB29-pQ-induced breast cancer metastasis in 4T1-luc cell inoculated nude mice is repressed by GLUT1 inhibition. Overall, our results demonstrated a novel mechanism that PCB29-pQ exposure promotes aerobic glycolysis in both in vitro and in vivo breast cancer models in a GLUT1-dependent fashion, which may provide a strategy to prevent breast cancer cell spread.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Female; Glycolysis; Mice; Mice, Nude; Polychlorinated Biphenyls; Quinones
PubMed: 34736186
DOI: 10.1016/j.jhazmat.2021.127512 -
Ecotoxicology and Environmental Safety May 2022Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated...
Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated foods, and thus the gastrointestinal system and gut microbiota are often exposed to high amounts of pollutants. Multiple studies have focused on the imbalance in intestinal microbiota composition caused by dioxin-like pollutants. Here, we examined the effects of polychlorinated biphenyl 126 (PCB126) on the composition and functions of gut microbes through metagenomic sequencing, and explored the correlations between microflora dysbiosis and aryl hydrocarbon receptor (AHR) signaling. Adult male wild-type and Ahr mice with a C57BL/6 background were weekly exposed to 50 μg/kg body weight of PCB126 for 8 weeks. Results showed that PCB126 had the opposite effect on gut microbiota composition and diversity in the wild-type and Ahr mice. Functional prediction found that PCB126 exposure mainly altered carbon metabolism and signal regulatory pathways in wild-type mice but impacted DNA replication and lipopolysaccharide biosynthesis in Ahr mice. In wild-type mice, PCB126 exposure induced liver injury, decreased serum lipid content, and delayed gastrointestinal motility, which were significantly correlated to several specific bacterial taxa, such as Helicobacter. Following AHR knockout, however, the holistic effects of PCB126 on the host were lessened or abolished. These results suggest that PCB126 may disrupt host metabolism and gut microbiota dynamics via AHR activation. Overall, our findings provide new insight into the complex interactions between host metabolism and gut microbiota, which may contribute to grouped assessment of environmental pollutants in the future.
Topics: Animals; Dioxins; Environmental Pollutants; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Receptors, Aryl Hydrocarbon
PubMed: 35367886
DOI: 10.1016/j.ecoenv.2022.113448 -
Environmental Geochemistry and Health Sep 2023Few studies have been conducted on spatial and temporal trends in polychlorinated naphthalenes (PCNs) in coastal environments. Here, we describe 18 PCN congeners found...
Few studies have been conducted on spatial and temporal trends in polychlorinated naphthalenes (PCNs) in coastal environments. Here, we describe 18 PCN congeners found in surface and dated sediment samples collected from highly industrialized bays of Korea. Measurable levels of PCN congeners were detected in all sediment samples, suggesting concurrent and historical contamination. The highest PCN concentrations were observed in sediment from rivers, streams, and the inner portions of the bays, which are surrounded by industrial complexes and commercial harbors. CNs 73, 66/67, and 52 were dominant in surface and dated sediment samples. Congener patterns and diagnostic ratios revealed that PCN contamination is originated from combustion processes and the use of polychlorinated biphenyl (PCB) technical mixtures. PCN concentrations in dated sediment increased from the 1980s to the mid-2000s and then decreased to 2015. Although the toxic equivalent (TEQ) levels of PCNs in our study did not exceed sediment quality guidelines proposed by international authorities, the cumulative risks from the TEQ concentrations of polychlorinated dibenzo-p-dioxins, furans, PCBs, and PCNs can be expected for benthic organisms.
Topics: Naphthalenes; Bays; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Republic of Korea
PubMed: 36151356
DOI: 10.1007/s10653-022-01395-6 -
Folia Microbiologica Aug 2021Unique bacterial associations were formed in the polluted soils from territory of the industrial factories Open Joint Stock Company "The Middle Volga Chemical Plant,"...
Unique bacterial associations were formed in the polluted soils from territory of the industrial factories Open Joint Stock Company "The Middle Volga Chemical Plant," Chapaevsk, Russia and Open Joint Stock Company "Lubricant Producing Plant," Perm, Russia. This study evaluates the influence of the biphenyl/polychlorinated biphenyls (PCB) on the formation of aerobic bacterial associations and their biodegradative potential. Enrichment cultivation of the soil samples from the territories of these industrial factories with PCB (commercial mixture Sovol) was lead for forming aerobic bacterial enrichment cultures showing a unique composition. The dominating in these bacterial cultures was the phylum Proteobacteria (Beta- and Gammaproteobacteria). Using biphenyl as a carbon source led to decrease of biodiversity in the final stable bacterial associations. Periodic cultivation experiments demonstrated that the association PN2-B has a high degradative potential among the six studied bacterial associations. PN2-B degraded 100% mono-chlorobiphenyls (94.5 mg/L), 86.2% di-chlorobiphenyls (22.3 mg/L), 50.9% Sovol, and 38.4% Delor 103 (13.8 mg/L). Qualitative analysis of metabolites showed that association performed transformation of chlorobenzoic acids (PCB degradation intermediates) into metabolites of citrate cycle. Twelve individual strain-destructors were isolated. The strains were found to degrade 17.7-100% PCB1, 36.2-100% PCB2, 18.8-100% PCB3 (94.5 mg/L), and 15.7-78.2% PCB8 (22.3 mg/L). The strains were shown to metabolize chlorobenzoic acids formed during degradation of chlorobiphenyls. A unique ability of strains Micrococcus sp. PNS1 and Stenotrophomonas sp. PNS6 to degrade ortho-, meta-, and para-monosubstituted chlorobenzoic acids was revealed. Our results suggest that PN2-B and individual bacterial strains will be perspective for cleaning of the environment from polychlorinated biphenyls.
Topics: Bacteria, Aerobic; Biodegradation, Environmental; Microbial Interactions; Polychlorinated Biphenyls; Soil Microbiology; Soil Pollutants
PubMed: 33966251
DOI: 10.1007/s12223-021-00873-1 -
Environmental Research Jan 2024Chinook salmon (Oncorhynchus tshawytscha) along the west coast of North America have experienced significant declines in abundance and body size over recent decades due...
Polychlorinated biphenyl and polybrominated diphenyl ether profiles vary with feeding ecology and marine rearing distribution among 10 Chinook salmon (Oncorhynchus tshawytscha) stocks in the North Pacific Ocean.
Chinook salmon (Oncorhynchus tshawytscha) along the west coast of North America have experienced significant declines in abundance and body size over recent decades due to several anthropogenic stressors. Understanding the reasons underlying the relatively high levels of persistent organic pollutants (POPs) in Chinook stocks is an important need, as it informs recovery planning for this foundation species, as well for the Chinook-dependent Resident killer whales (Orcinus orca, RKW) of British Columbia (Canada) and Washington State (USA). We evaluated the influence of stock-related differences in feeding ecology, using stable isotopes, and marine rearing ground on the concentrations and patterns of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in Chinook salmon. A principal components analysis (PCA) revealed a clear divergence of PCB and PBDE congener patterns between Chinook with a nearshore rearing distribution ('shelf resident') versus a more offshore distribution. Shelf resident Chinook had 12-fold higher PCB concentrations and 46-fold higher PBDE concentrations relative to offshore stocks. Shelf resident Chinook had PCB and PBDE profiles that were heavier and dominated by more bioaccumulative congeners, respectively. The higher δC and δN in shelf resident Chinook compared to the offshore rearing stocks, and their different marine distributions explain the large divergence in contaminant levels and profiles, with shelf resident stocks being heavily influenced by land-based sources of industrial contamination. Results provide compelling new insight into the drivers of contaminant accumulation in Chinook salmon, raise important questions about the consequences for their health, and explain a major pathway to the heavily POP-contaminated Resident killer whales that consume them.
Topics: Animals; Polychlorinated Biphenyls; Salmon; Halogenated Diphenyl Ethers; Pacific Ocean; Whale, Killer; British Columbia
PubMed: 37879388
DOI: 10.1016/j.envres.2023.117476 -
Environmental Science & Technology Oct 2022We conducted experiments to determine whether bioaugmentation with aerobic, polychlorinated biphenyl (PCB)-degrading microorganisms can mitigate polychlorinated biphenyl...
We conducted experiments to determine whether bioaugmentation with aerobic, polychlorinated biphenyl (PCB)-degrading microorganisms can mitigate polychlorinated biphenyl (PCB) emissions from contaminated sediment to air. strain LB400 was added to bioreactors containing PCB-contaminated site sediment. PCB mass in both the headspace and aqueous bioreactor compartments was measured using passive samplers over 35 days. Time-series measurements of all 209 PCB congeners revealed a 57% decrease in total PCB mass accumulated in the vapor phase of bioaugmented treatments relative to non-bioaugmented controls, on average. A comparative congener-specific analysis revealed preferential biodegradation of lower-chlorinated PCBs (LC-PCBs) by LB400. Release of the most abundant congener (PCB 4 [2,2'-dichlorobiphenyl]) decreased by over 90%. Simulations with a PCB reactive transport model closely aligned with experimental observations. We also evaluated the effect of the phytogenic biosurfactant, saponin, on PCB bioavailability and biodegradation by LB400. Time-series qPCR measurements of biphenyl dioxygenase () genes showed that saponin better maintained abundance, compared to the saponin-free treatment. These findings indicate that an active population of bioaugmented, aerobic PCB-degrading microorganisms can effectively lower PCB emissions and may therefore contribute to minimizing PCB inhalation exposure in communities surrounding PCB-contaminated sites.
Topics: Biodegradation, Environmental; Dioxygenases; Hydroxylamines; Polychlorinated Biphenyls
PubMed: 36178372
DOI: 10.1021/acs.est.2c01043