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European Thyroid Journal Jun 2024The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort.
OBJECTIVE
The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort.
METHODS
We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods.
RESULTS
The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180.
CONCLUSION
Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.
Topics: Humans; Case-Control Studies; Fluorocarbons; Female; Male; Middle Aged; Endocrine Disruptors; Thyroid Neoplasms; Polychlorinated Biphenyls; Alkanesulfonic Acids; Adult; Persistent Organic Pollutants; Aged; Dichlorodiphenyl Dichloroethylene; Decanoic Acids; DDT; Italy; Caprylates; Proto-Oncogene Proteins B-raf; Fatty Acids; Sulfonic Acids; Mutation; Environmental Exposure
PubMed: 38657654
DOI: 10.1530/ETJ-23-0192 -
Journal of the American Society For... May 2024Identification of stereo- and positional isomers detected with high-resolution mass spectrometry (HRMS) is often challenging due to near-identical fragmentation spectra...
Identification of stereo- and positional isomers detected with high-resolution mass spectrometry (HRMS) is often challenging due to near-identical fragmentation spectra (MS), similar retention times, and collision cross-section values (CCS). Here we address this challenge on the example of hydroxylated polychlorinated biphenyls (OH-PCBs) with the aim to (1) distinguish between isomers of OH-PCBs using two-dimensional ion mobility spectrometry (2D-IMS) and (2) investigate the structure of the fragments of OH-PCBs and their fragmentation mechanisms by ion mobility spectrometry coupled to high-resolution mass spectrometry (IMS-HRMS). The MS spectra as well as CCS values of the deprotonated molecule and fragment ions were measured for 18 OH-PCBs using flow injections coupled to a cyclic IMS-HRMS. The MS spectra as well as the CCS values of the parent and fragment ions were similar between parent compound isomers; however, ion mobility separation of the fragment ions is hinting at the formation of isomeric fragments. Different parent compound isomers also yielded different numbers of isomeric fragment mobilogram peaks giving new insights into the fragmentation of these compounds and indicating new possibilities for identification. For spectral interpretation, Gibbs free energies and CCS values for the fragment ions of 4'-OH-CB35, 4'-OH-CB79, 2-OH-CB77 and 4-OH-CB107 were calculated and enabled assignment of structures to the isomeric mobilogram peaks of [M-H-HCl] fragments. Finally, further fragmentation of the isomeric fragments revealed different fragmentation pathways depending on the isomeric fragment ions.
PubMed: 38640444
DOI: 10.1021/jasms.4c00035 -
Environmental Research Jul 2024The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood...
UNLABELLED
The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence.
METHODS
The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms.
RESULTS
The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 μg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction.
CONCLUSION
Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted.
Topics: Humans; Female; Mercury; Spain; Pregnancy; Prenatal Exposure Delayed Effects; Child, Preschool; Child; Male; Fetal Blood; Longitudinal Studies; Environmental Pollutants; Birth Cohort; Adult; Cohort Studies; Maternal Exposure
PubMed: 38631469
DOI: 10.1016/j.envres.2024.118954 -
Environmental Health Perspectives Apr 2024Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that...
BACKGROUND
Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD).
OBJECTIVE
To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses.
METHODS
Briefly, male C57BL/6J mice were exposed to polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification.
RESULTS
Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice.
DISCUSSION
Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.
Topics: Male; Mice; Animals; Multiomics; Mice, Inbred C57BL; Ethanol; Liver; Polychlorinated Biphenyls; Fatty Liver; Liver Diseases, Alcoholic; Environmental Pollutants; Zinc; Tyrosine
PubMed: 38619879
DOI: 10.1289/EHP14132 -
Chemosphere Jun 2024Polychlorinated biphenyls (PCBs) are a primary contaminant of potential concern at the Newtown Creek superfund site. Measurements of PCBs in hundreds of samples of...
Polychlorinated biphenyls (PCBs) are a primary contaminant of potential concern at the Newtown Creek superfund site. Measurements of PCBs in hundreds of samples of sediment (surface and cores) within Newtown Creek and at nearby reference locations were obtained from the Remedial Investigation (RI) databases. This data set was analyzed using Positive Matrix Factorization (PMF). A weight-of-evidence approach was used to attribute the PMF-generated fingerprints to sources. The PMF analysis generated eight factors (fingerprints or sources) that represent primary sources, such as Aroclors, as well as secondary sources, including the East River and Combined Sewer Outfalls (CSOs). In addition to the high-production volume Aroclors (1016/1242, 1248, 1254, and 1260), some less-widely used Aroclors (1232 and 1268) were found in Newtown Creek sediment. Aroclor 1268 is disproportionately abundant in the deepest sediments, while PCBs likely from CSOs are relatively more abundant in surface sediment.
Topics: Polychlorinated Biphenyls; Geologic Sediments; Environmental Monitoring; Water Pollutants, Chemical; Aroclors; Rivers
PubMed: 38615951
DOI: 10.1016/j.chemosphere.2024.141928 -
Environment International Apr 2024The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the...
The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T] and thyroxine [T]), and their metabolites reverse T and 3,5-diiodothyronine [3,5-T]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T, rT and 3,5-T. Specifically, there was a weak significant negative association between T and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T and ΣPBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.
Topics: Animals; Female; Male; Water Pollutants, Chemical; Hydrocortisone; Thyroid Hormones; Beluga Whale; Estuaries; Halogenated Diphenyl Ethers; Polychlorinated Biphenyls; Environmental Monitoring; Flame Retardants; Stress, Physiological; Endangered Species; Triiodothyronine; Hydrocarbons, Halogenated; Thyroxine
PubMed: 38615542
DOI: 10.1016/j.envint.2024.108647 -
Environment International Apr 2024The eagle owl (Bubo bubo) population in Norway is today classified as critically endangered on the red list of endangered species. Because previous studies have detected...
The eagle owl (Bubo bubo) population in Norway is today classified as critically endangered on the red list of endangered species. Because previous studies have detected high concentrations of Persistent Organic Pollutants (POPs) in birds of prey, concerns have been raised whether POPs exposure are a significant factor to the substantial decline of the eagle owl population. The aims of this study were to measure the levels of POPs in eagle owls and to assess whether POPs may represent a potential health risk. POPs were analysed in liver samples from 100 eagle owls collected between 1994 and 2014. The concentrations of POPs were generally very high and individual birds had levels among the highest measured worldwide. The contaminant groups analysed were highly correlated (p < 0.0001). The concentrations of sum of Polychlorinated Biphenyls (∑PCB) exceeded the threshold value from moderate to severe health risk in 90% of the birds. The birds with cachectic or lean body condition had significantly higher levels of contaminants than those with higher body condition scores. No significant temporal or spatial trends were noted. The lack of temporal trends, suggest that the downward trend of POPs, appear to be levelling off. The lack of differences between inland and coastal regions suggest that the risk of exposure may be comparable between predatory birds feeding in marine or terrestrial food webs. The significantly higher POPs levels detected in individuals with poor body condition may be due to reduced fat stores and thereby higher concentration in the remaining fat and/or the weight loss could be induced by toxic effects. The high proportion of birds exceeding the threshold values for severe and high risk of adverse effects, suggest that the high contamination load may reduce the eagle owl's fitness and survival and, thus, contribute to decline of the eagle owl population.
Topics: Animals; Strigiformes; Norway; Environmental Pollutants; Endangered Species; Polychlorinated Biphenyls; Environmental Exposure; Environmental Monitoring; Liver; Female; Male; Risk Assessment
PubMed: 38613936
DOI: 10.1016/j.envint.2024.108650 -
Scientific Reports Apr 2024This study investigated the association between serum concentrations of Polychlorinated Biphenyls (PCBs) and the risk of type 2 diabetes within the general population. A...
This study investigated the association between serum concentrations of Polychlorinated Biphenyls (PCBs) and the risk of type 2 diabetes within the general population. A ten-year follow-up historical cohort study was conducted during 2009-2019 as part of the Bushehr MONICA cohort study in Iran. Of 893 non-diabetes participants at base line, 181 individuals were included in the study. The concentration of nine PCB congeners was measured in individuals' serum samples at baseline, and the risk of type 2 diabetes was determined based on fasting blood sugar at the end of follow-up. Multiple logistic regression models were used to assess the study outcomes after adjusting for covariates. This study included 59 diabetes individuals (32.6%; mean [SD] age: 58.64 [8.05]) and 122 non-diabetes individuals (67.4%; mean [SD] age: 52.75 [8.68]). Multivariable analysis revealed that a one-tertile increase (increasing from 33rd centile to 67th centile) in Σ non-dioxin-like-PCBs (OR 2.749, 95% CI 1.066-7.089), Σ dioxin-like-PCBs (OR 4.842, 95% CI 1.911-12.269), and Σ PCBs (OR 2.887, 95% CI 1.120-7.441) significantly associated with an increased risk of type 2 diabetes. The strongest association was obtained for dioxin-like PCBs. The results highlight a significant correlation between PCB exposure and an increased risk of type 2 diabetes. The evidence suggests that additional epidemiological studies are necessary to clarify the link between PCBs and diabetes.
Topics: Humans; Middle Aged; Diabetes Mellitus, Type 2; Polychlorinated Biphenyls; Cohort Studies; Dioxins; Follow-Up Studies; Polychlorinated Dibenzodioxins
PubMed: 38609448
DOI: 10.1038/s41598-024-59308-9 -
Environment International Apr 2024Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by genetic factors and environmental exposures. Polychlorinated biphenyls (PCBs), a group of...
Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by genetic factors and environmental exposures. Polychlorinated biphenyls (PCBs), a group of synthetic organic compounds, have been identified as potential environmental risk factors for neurodegenerative diseases, including PD. We explored PCB-induced neurotoxicity mechanisms using iPSC-derived dopaminergic neurons and assessed their transcriptomic responses to varying PCB concentrations (0.01 μM, 0.5 μM, and 10 μM). Specifically, we focused on PCB-180, a congener known for its accumulation in human brains. The exposure durations were 24 h and 74 h, allowing us to capture both short-term and more prolonged effects on gene expression patterns. We observed that PCB exposure led to the suppression of oxidative phosphorylation, synaptic function, and neurotransmitter release, implicating these pathways in PCB-induced neurotoxicity. In our comparative analysis, we noted similarities in PCB-induced changes with other PD-related compounds like MPP+ and rotenone. Our findings also aligned with gene expression changes in human blood derived from a population exposed to PCBs, highlighting broader inflammatory responses. Additionally, molecular patterns seen in iPSC-derived neurons were confirmed in postmortem PD brain tissues, validating our in vitro results. In conclusion, our study offers novel insights into the multifaceted impacts of PCB-induced perturbations on various cellular contexts relevant to PD. The use of iPSC-derived dopaminergic neurons allowed us to decipher intricate transcriptomic alterations, bridging the gap between in vitro and in vivo findings. This work underscores the potential role of PCB exposure in neurodegenerative diseases like PD, emphasizing the need to consider both systemic and cell specific effects.
Topics: Polychlorinated Biphenyls; Parkinson Disease; Dopaminergic Neurons; Humans; Transcriptome; Blood Cells; Induced Pluripotent Stem Cells; Environmental Pollutants
PubMed: 38608384
DOI: 10.1016/j.envint.2024.108642 -
Journal of Parkinson's Disease 2024The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric... (Review)
Review
The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson's disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson's disease and open the door toward the ultimate goal -prevention.
Topics: Humans; Parkinson Disease; Environmental Exposure; Brain; Lewy Body Disease; alpha-Synuclein
PubMed: 38607765
DOI: 10.3233/JPD-240019