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Environmental Toxicology Sep 2015Polychlorinated biphenyl (PCB) quinones are known to cause toxic effects, but their mechanisms are quite unclear. In this study, we examined whether...
Polychlorinated biphenyl (PCB) quinones are known to cause toxic effects, but their mechanisms are quite unclear. In this study, we examined whether 2,3,5-trichloro-6-phenyl-[1,4]benzoquinone, PCB29-pQ, induces cell death via apoptosis pathway. Our result showed PCB29-pQ exposure decreased HepG2 cell viability in a time-dependent manner. Lactate dehydrogenase leakage assay also implied the cytotoxicity of PCB29-pQ. 4',6-Diamidino-2-phenylindole dihydrochloride staining and flow cytometry assays both confirmed PCB29-pQ caused dose-dependent apoptotic cell death in HepG2 cells. Furthermore, we found that PCB29-pQ exposure increased cellular reactive oxygen species (ROS) level, decreased mitochondrial membrane potential and induced the translocation of cytochrome c from mitochondria into cytosol in HepG2 cells. Moreover, PCB29-pQ exposure induced B-cell lymphoma 2 (Bcl-2) downregulation and Bcl-2-associated X (Bax) upregulation, poly(ADP-ribose) polymerase cleavage, accompanied with the increased caspase-3/9 and p53 expressions. Taking together, these results suggested PCB29-pQ induced HepG2 cells apoptosis through a ROS-driven, mitochondrial-mediated and caspase-dependent pathway.
Topics: Apoptosis; Benzoquinones; Caspase 3; Caspase 9; Cytochromes c; Hep G2 Cells; Humans; Membrane Potential, Mitochondrial; Mitochondria; Poly(ADP-ribose) Polymerases; Polychlorinated Biphenyls; Reactive Oxygen Species; Tumor Suppressor Protein p53; Up-Regulation; bcl-2-Associated X Protein
PubMed: 24604693
DOI: 10.1002/tox.21979 -
Chemical Research in Toxicology Sep 2021Exposure to polychlorinated biphenyls (PCBs) is implicated in adverse neurotoxic outcomes. However, the impact of PCBs on the adolescent nervous system has received... (Review)
Review
Exposure to polychlorinated biphenyls (PCBs) is implicated in adverse neurotoxic outcomes. However, the impact of PCBs on the adolescent nervous system has received inadequate attention. We conducted a comprehensive review to identify studies of neurotoxic outcomes following PCB exposure during the adolescent period in rodents. Only four papers were found to meet all inclusion criteria. PCB exposure in adolescent rats caused disruptions in the main functions of the prefrontal cortex, resulting in cognitive deficits. This comprehensive review demonstrates that more research is needed to characterize how PCB exposure adversely affects the adolescent nervous system.
Topics: Adolescent; Animals; Humans; Nervous System; Polychlorinated Biphenyls
PubMed: 34491731
DOI: 10.1021/acs.chemrestox.1c00226 -
Environment International Aug 2015Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer...
Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer dismantling plant. This was undertaken to identify sources of exposure and investigate changes to the PCB signature and EFs over different exposure periods. Approximately 1.5 g of serum was extracted and PCB signatures were created through analysis by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS) and EFs calculated following analysis by gas chromatography with high resolution mass spectrometry (GC-HRMS). A total of 84 PCBs were identified in the serum samples with concentrations of the 7 indicator PCBs ranging from 11-350 ng g(-1) of serum (1.2-39 μg g(-1) lipid). The PCB signatures were interpreted using principal component analysis (PCA) which was able to distinguish workers with background or recent minimal exposure from those with prolonged occupational exposure. Occupationally exposed individuals had a similar PCB profile to Aroclor A1260. However, individuals with prolonged exposure had depleted proportions of several PCB congeners that are susceptible to metabolism (CB-95, CB-101 and CB-151) and elevated proportions of PCBs that are resistant to metabolism (CB-74, CB-153, CB-138 and CB-180). The results also identified a third group of workers with elevated proportions of CB-28, CB-60, CB-66, CB-74, CB-105 and CB-118 who appeared to have been exposed to an additional source of PCBs. The results show near complete removal of the CB-95 E2 enantiomer in some samples, indicating that bioselective metabolism or preferential excretion of one enantiomer occurs in humans. By considering PCB concentrations along with detailed congener specific signatures it was possible to identify different exposure sources, and gain an insight into both the magnitude and duration of exposure.
Topics: Environmental Pollutants; Gas Chromatography-Mass Spectrometry; Humans; Occupational Exposure; Polychlorinated Biphenyls; Principal Component Analysis; Stereoisomerism
PubMed: 25916940
DOI: 10.1016/j.envint.2015.04.006 -
Environmental Toxicology and Chemistry Aug 2021Bioaccumulation of hydrophobic pollutants in an aquatic food web is governed by exposure concentrations in sediment and water phases and by complex trophic interactions...
Bioaccumulation of hydrophobic pollutants in an aquatic food web is governed by exposure concentrations in sediment and water phases and by complex trophic interactions among the various species. We demonstrate that biological interactions and exposure from the chemical environment can be deconvoluted for aquatic food webs to allow clearer assessments of the role of thermodynamic drivers from the sediment and surface water phases. We first demonstrate the feasibility of this deconvolution mathematically for hypothetical food webs with 3 and 4 interacting species and for more realistic real-world food webs with >10 species of aquatic organisms (i.e., the freshwater lake food web in Western Lake Erie [ON, Canada] and the marine food web in New Bedford Harbor [MA, USA]). Our results show both mathematically (for the simple food webs) and computationally (for the more complex food webs) that a deconvoluted food web model parameterized for site-specific conditions can predict the bioaccumulation of polychlorinated biphenyls in aquatic organisms same as existing complex food web models. The merit of this approach is that once the thermodynamic and biological contributions to food web bioaccumulation are computed for an ecosystem, the deconvoluted model provides a relatively simple approach for calculating concentrations of chemicals in organisms for a range of possible surface water and sedimentary concentrations. This approach is especially useful for calculating bioaccumulation of pollutants from freely dissolved concentrations measured using passive sampling devices or predicted by fate and transport models. The deconvoluted approach makes it possible to develop regulatory guidelines for a set of surface water and sediment (or porewater) concentration combinations for a water body that is able to achieve a risk-based target for fish concentration. Environ Toxicol Chem 2021;40:2145-2155. © 2021 SETAC.
Topics: Animals; Aquatic Organisms; Biology; Ecosystem; Environmental Monitoring; Environmental Pollutants; Fishes; Food Chain; Lakes; Polychlorinated Biphenyls; Thermodynamics; Water; Water Pollutants, Chemical
PubMed: 33930216
DOI: 10.1002/etc.5106 -
Scientific Reports Mar 2019A temporal decline in human and dog sperm quality is thought to reflect a common environmental aetiology. This may reflect direct effects of seminal chemicals on sperm...
A temporal decline in human and dog sperm quality is thought to reflect a common environmental aetiology. This may reflect direct effects of seminal chemicals on sperm function and quality. Here we report the effects of diethylhexyl phthalate (DEHP) and polychlorinated biphenyl 153 (PCB153) on DNA fragmentation and motility in human and dog sperm. Human and dog semen was collected from registered donors (n = 9) and from stud dogs (n = 11) and incubated with PCB153 and DEHP, independently and combined, at 0x, 2x, 10x and 100x dog testis concentrations. A total of 16 treatments reflected a 4 × 4 factorial experimental design. Although exposure to DEHP and/or PCB153 alone increased DNA fragmentation and decreased motility, the scale of dose-related effects varied with the presence and relative concentrations of each chemical (DEHP.PCB interaction for: DNA fragmentation; human p < 0.001, dog p < 0.001; Motility; human p < 0.001, dog p < 0.05). In both human and dog sperm, progressive motility negatively correlated with DNA fragmentation regardless of chemical presence (Human: P < 0.0001, r = -0.36; dog P < 0.0001, r = -0.29). We conclude that DEHP and PCB153, at known tissue concentrations, induce similar effects on human and dog sperm supporting the contention of the dog as a sentinel species for human exposure.
Topics: Animals; DNA Fragmentation; Diethylhexyl Phthalate; Dogs; Environmental Exposure; Humans; Male; Polychlorinated Biphenyls; Semen Analysis; Sperm Motility; Spermatozoa; Testis
PubMed: 30833626
DOI: 10.1038/s41598-019-39913-9 -
Chemical Research in Toxicology Jun 2015Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with...
Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is an organelle responsible for protein folding and calcium storage. ER stress leads to the accumulation of unfolded proteins in the ER lumen. To be against or respond to this effect, cells have a comprehensive signaling system, called unfolded protein response (UPR), to restore homeostasis and normal ER function or activate the cell death program. Therefore, it is critical to understand how environmental insult regulates the ingredients of ER stress and UPR signalings. Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2 cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress, UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed PCB29-pQ induced ER morphological defects by using transmission electron microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and calpain activity, which were significantly inhibited by the pretreatment of BAPTA-AM (Ca(2+) chelator). These results were correlated with the outcome that PCB29-pQ induces ER stress-related apoptosis through caspase family gene 12, while salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS formation and consequently alleviated PCB29-pQ-induced expression of ER stress-related genes. In conclusion, our result demonstrated for the first time that PCB quinone leads to ROS-dependent induction of ER stress, and UPR and calcium release in HepG2 cells, and the evaluation of the perturbations of ER stress, UPR, and calcium signaling provide further information on the mechanisms of PCB-induced toxicity.
Topics: Apoptosis; Benzoquinones; Calcium; Dose-Response Relationship, Drug; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Hep G2 Cells; Humans; Molecular Structure; Polychlorinated Biphenyls; Protein Unfolding; Reactive Oxygen Species; Signal Transduction; Structure-Activity Relationship; Time Factors; Transcription Factor CHOP; Tumor Cells, Cultured; Unfolded Protein Response
PubMed: 25950987
DOI: 10.1021/acs.chemrestox.5b00124 -
Reviews on Environmental Health Mar 2022Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a... (Review)
Review
Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a variety of chemicals including, dioxins, organochlorines (OCs), polychlorinated biphenyl (PCBs), and perfluoroalkyl substances (PFASs) that contain a long half-life and highly resistant to biodegradation. These environmental pollutants accumulate over time in adipose tissues of living organisms and alter various insulin function-related genes. Childhood Metabolic Syndrome (MetS) consists of multiple cardiovascular risk factors, insulin function being one of them. Over the years, the incidence of the syndrome has increased dramatically. It is imperative to explore the role of persistent organic pollutants in the development of Childhood Metabolic Syndrome. Some epidemiological studies have reported an association between prenatal exposure to POPs and offspring MetS development throughout childhood. These findings have been replicated in animal studies in which these pollutants exercise negative health outcomes such as obesity and increased waist circumference. This review discusses the role of prenatal exposure to POPs among offspring who develop MetS in childhood, the latest research on the MetS concept, epidemiological and experimental findings on MetS, and the POPs modes of action. This literature review identified consistent research results on this topic. Even though the studies in this review had many strengths, one major weakness was the usage of different combinations of MetS criteria to measure the outcomes. These findings elucidate the urgent need to solidify the pediatric MetS definition. An accurate definition will permit scientists to measure the MetS as a health outcome properly and allow clinicians to diagnose pediatric MetS and provide individualized treatment appropriately.
Topics: Animals; Environmental Pollutants; Female; Humans; Metabolic Syndrome; Persistent Organic Pollutants; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 33866704
DOI: 10.1515/reveh-2020-0113 -
Journal of Food Protection Mar 2024Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine...
Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.
Topics: Humans; Polychlorinated Biphenyls; Fish Oils; Japan; Dietary Supplements; Body Weight; Food Contamination
PubMed: 38301956
DOI: 10.1016/j.jfp.2024.100235 -
Environmental Monitoring and Assessment Jan 2023Few studies have been performed on the persistent organic pollutant contamination in soil from the plateau and remote areas, particularly the mid-latitude arid and...
Few studies have been performed on the persistent organic pollutant contamination in soil from the plateau and remote areas, particularly the mid-latitude arid and semi-arid regions of Northwest China. The occurrence, spatial distribution, source, and potential risk of 12 polychlorinated biphenyls (PCBs) were investigated in soil collected from five Hexi Corridor cities in Northwest China. All of the PCBs were detected individually in the soil samples. The concentration of ΣPCBs in the Hexi Corridor ranged from 2.0 to 148.5 ng/g, with an average of 21.3 ng/g. The tetra-CBs and hexa-CBs were the dominant PCB components in the soil. Higher PCB levels were found in the industrial city of Jiuquan, and the fewest PCBs were detected at Jinchang. Source analysis by principal component analysis showed that the dominant sources of PCBs were automobile exhaust, paint additives, insulation materials, and other industrial products. The carcinogenic health risk of PCBs in the Hexi Corridor soil was within acceptable levels, but the exposure risk of PCBs in soil for children was higher than that for adults.
Topics: Child; Humans; Polychlorinated Biphenyls; Cities; Soil; Soil Pollutants; Environmental Monitoring; China
PubMed: 36622457
DOI: 10.1007/s10661-022-10891-2 -
Journal of Agricultural and Food... Jun 2022Polychlorinated biphenyls (PCBs) can be metabolized into hydroxylated PCBs (OH-PCBs) that exhibit greater toxicity than their parent compounds. In particular,...
Polychlorinated biphenyls (PCBs) can be metabolized into hydroxylated PCBs (OH-PCBs) that exhibit greater toxicity than their parent compounds. In particular, 2,2',4,5,5'-pentachlorobiphenyl (PCB 101) is commonly found in chicken feeds and breeding environments, although information on the biotransformation of this PCB in chickens is lacking. In this study, the hydroxylation metabolization of PCB 101 was assessed based on in vitro trials with Sanhuang chicken liver microsomes and in vivo experiments with Hy-Line Brown hens. The -substituted metabolite 4'-OH-PCB 101 is the predominant metabolite of PCB 101. 4'-OH-PCB 101 is preferentially retained in the chicken bloodstream and partly distributed into different tissues of laying hens. The blood-brain barrier can effectively prevent the OH-PCB from entering the brain, and the adipose tissue contains a relatively low residue concentration of the OH-PCB. The laying hen can deplete the OH-PCB via laying eggs and excrement. The ratio of 4'-OH-PCB 101/PCB 101 in egg yolk is about 1:2. These results first provide definite evidence for the previous hypothesis of the PCB 101 metabolism by chickens. They could assist in predicting the environmental fate of PCBs, and in the risk assessment of PCBs and OH-PCBs in chicken-based foodstuffs.
Topics: Animals; Chickens; Female; Hydroxylation; Microsomes, Liver; Pilot Projects; Polychlorinated Biphenyls
PubMed: 35649149
DOI: 10.1021/acs.jafc.2c01462