Effects of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) on Arabidopsis thaliana.
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE99345 | GEO | 2017/06/15
SECONDARY ACCESSION(S): PRJNA388167
REPOSITORIES: GEO
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Project description:Plants metabolize polychlorinated biphenyls (PCBs) into hydroxylated derivatives (OH-PCBs), which are sometimes more toxic than the parent PCBs. The objective of this research was to compare the toxicity of a suite of PCBs and OH-PCBs toward the model plant, Arabidopsis thaliana. While parent PCBs and higher-chlorinated OH-PCBs exhibited a low or nondetectable toxicity, lower-chlorinated OH-PCBs significantly inhibited the germination rate and plant growth, with inhibition concentration 50% (IC50) ranging from 1.6 to 12.0 mg L-1. The transcriptomic response of A. thaliana to 2,5-dichlorobiphenyl (2,5-DCB), and its OH metabolite, 4'-OH-2,5-DCB, was then examined using whole-genome expression microarrays (Affymetrix). Exposure to 2,5-DCB and 4'-OH-2,5-DCB resulted in different expression patterns, with the former leading to enrichment of genes involved in response to toxic stress and detoxification functions. Exposure to 2,5-DCB induced multiple xenobiotic response genes, such as cytochrome P-450 and glutathione S-transferases, potentially involved in the PCB metabolism. On the contrary, exposure to both compounds resulted in the down-regulation of genes involved in stresses not directly related to toxicity. Unlike its OH derivative, 2,5-DCB was shown to induce a transcriptomic profile similar to plant safeners, which are nontoxic chemicals stimulating detoxification pathways in plants. The differentiated induction of detoxification enzymes by 2,5-DCB may explain its lower phytotoxicity compared to 4'-OH-2,5-DCB.
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Project description:Hydroxylated polychlorinated biphenyls (OH-PCBs) are toxic contaminants produced by biotic or abiotic transformation of PCBs. In this study, we have tested the toxicity of 2,5-dichlorobiphenyl (2,5-DCB) and three of its OH-derivatives, 2'-OH-, 3'-OH-, and 4'-OH-2,5-DCB toward the model plant, Arabidopsis thaliana. Toxicity tests showed that the parent 2,5-DCB (5 mg L-1) had little effect on the plants, while all three OH-metabolites (5 mg L-1) exhibited a significant toxicity, with 4'-OH-2,5-DCB being the most potent (inhibition concentration 50%-IC50 in germination tests = 9.8 mg L-1 for 2'-OH-2,5-DCB, 9.5 mg L-1 for 3'-OH-2,5-DCB, and 4.8 mg L-1 for 4'-OH-2,5-DCB). Whole-genome expression microarrays (Affymetrix) showed that exposure to the three OH-PCBs resulted in rather similar expression patterns, which were distinct from the one developing in response to 2,5-DCB. Searching an Arabidopsis microarray database (Genevestigator) revealed that, unlike the parent compound, the three OH-derivatives induced expression profiles similar to inhibitors of brassinosteroid synthesis (i.e., brassinazole, propiconazole, and uniconazole), resulting in severe iron deficiency in exposed plants. Our results suggest that the higher phytotoxicity of OH-derivatives as compared to 2,5-DCB is at least partly explained by the inhibition of the brassinosteroid pathway.
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Project description:In a sample of 442 births from the Child Health and Development Studies cohort, we examined associations between maternal prenatal exposure to hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) and pregnancy outcomes, and whether associations were mediated by maternal thyroid hormone levels and/or modified by maternal smoking. Compared to nonsmokers, smokers had twice the mean concentration of 4-OH-CB107 (p<0.001) and lower levels of its parent compound, PCB118 (p=0.001). Among mothers who smoked, the birth weight of newborns with maternal concentrations of 4-OH-CB107 in the upper quartile was 316g lighter (95% confidence interval (CI) 566, 65) compared to those with maternal concentrations in the lowest quartile, after control for PCB118 and other potential confounders. This association was not observed for non-smoking mothers and was not mediated by maternal thyroid hormone levels. Maternal prenatal 4-OH-CB107 levels appear to be influenced by maternal smoking and contribute to lower birth weight among smokers.
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Project description:Polychlorinated biphenyls (PCBs) are an important group of environmental pollutants that have been associated with adverse human health effects. Despite recent advances in their synthesis, the availability of PCB congeners in sufficient quantity and purity still represents one obstacle in the investigation of their biological effects. We report herein improved syntheses of PCB congeners (and their metabolites) containing two or more ortho-chlorine substituents. The Suzuki coupling reaction at 110 °C yielded PCB congeners with a 2,2'-substitution pattern in good yields (78-99%), but failed to give PCB congeners with 3 or 4 ortho chlorine substituents. Symmetrically substituted PCB congeners with multiple ortho chlorine substituents were obtained in 20-52% yields using a modified Ullmann coupling reaction. The yield of the coupling increased with increasing degree of chlorination of the starting material. The modified Ullmann coupling reaction employed much milder reaction conditions (copper-bronze/CuCl in N-methylpyrrolidinone, 110 °C) and, therefore, appears to be advantageous compared to the classical Ullmann coupling reaction (copper-bronze, no solvent, 230 °C). PCBs 136 and 155 prepared via the modified Ullmann coupling reaction were nitrated and reduced with Na(2)S(2)O(4) to the corresponding amino-PCBs. Subsequently, the amino-PCBs were converted into sulfur-containing PCB metabolites or PCB 184 via the corresponding diazonium salt. These modified reaction conditions allow the synthesis of large quantities of pure, non-dioxin-like PCB congeners and their sulfur-containing metabolites for environmental and toxicological studies by overcoming problems associated with classical PCB synthesis strategies.
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Project description:Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1-2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals.
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Project description:PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.
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Project description:Polychlorinated biphenyls (PCBs), a class of hazardous pollutants, are difficult to dissipate in the natural environment. In this study, a cyanobacterial strain Anabaena PD-1 showed good resistance against PCB congeners. Compared to a control group, chlorophyll a content decreased 3.7% and 11.7% when Anabaena PD-1 was exposed to 2 and 5 mg/L PCBs for 7 d. This cyanobacterial strain was capable of decomposing PCB congeners which was conclusively proved by determination of chloride ion concentrations in chlorine-free medium. After 7 d, the chloride ion concentrations in PCB-treated groups (1, 2, 5 mg/L) were 3.55, 3.05, and 2.25 mg/L, respectively. The genetic information of strain PD-1 was obtained through 16S rRNA sequencing analysis. The GenBank accession number of 16S rRNA of Anabaena PD-1 was KF201693.1. Phylogenetic tree analysis clearly indicated that Anabaena PD-1 belonged to the genus Anabaena. The degradation half-life of Aroclor 1254 by Anabaena PD-1 was 11.36 d; the total degradation rate for Aroclor 1254 was 84.4% after 25 d. Less chlorinated PCB congeners were more likely to be degraded by Anabaena PD-1 in comparison with highly chlorinated congeners. Meta- and para-chlorines in trichlorodiphenyls and tetrachlorobiphenyls were more susceptible to dechlorination than ortho-chlorines during the PCB-degradation process by Anabaena PD-1. Furthermore, Anabaena PD-1 can decompose dioxin-like PCBs. The percent biodegradation of 12 dioxin-like PCBs by strain PD-1 ranged from 37.4% to 68.4% after 25 days. Results above demonstrate that Anabaena PD-1 is a PCB-degrader with great potential for the in situ bioremediation of PCB-contaminated paddy soils.
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