Effects of polycyclic aromatic hydrocarbons on osteoclasts and osteoblasts in the scales of zebrafish
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE161253 | GEO | 2020/11/12
REPOSITORIES: GEO
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Project description:Assessing the potential carcinogenicity of human toxins represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk with limited reliability, and are expensive and time-consuming. To identify alternative prediction methods, we evaluated a transcriptomics-based human in vitro model to classify carcinogens by their modes of action. The aim of this study was to determine the transcriptomic response and identify specific molecular signatures of polycyclic aromatic hydrocarbons (PAHs), which can be used as predictors of carcinogenicity of environmental toxins in human in vitro systems. We found that characteristic molecular signatures facilitate identification and prediction of carcinogens. To evaluate the change in gene expression levels, human hepatocellular carcinoma (HepG2) cells were exposed to nine different PAHs (benzo[a]pyrene, dibenzo[a,h]anthracene, 3-methylcholanthrene, naphthalene, chrysene, phenanthrene, benzo[a]anthracene, benzo[k]fluoranthene, and indeno[1,2,3-c,d]pyrene) for 48 h. Gene expression analysis was conducted using a 44K whole human genome microarray (Agilent Technologies, USA).
2012-04-17 | E-GEOD-37326 | biostudies-arrayexpress
Project description:Assessing the potential carcinogenicity of human toxins represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk with limited reliability, and are expensive and time-consuming. To identify alternative prediction methods, we evaluated a transcriptomics-based human in vitro model to classify carcinogens by their modes of action. The aim of this study was to determine the transcriptomic response and identify specific molecular signatures of polycyclic aromatic hydrocarbons (PAHs), which can be used as predictors of carcinogenicity of environmental toxins in human in vitro systems. We found that characteristic molecular signatures facilitate identification and prediction of carcinogens.
2012-04-18 | GSE37326 | GEO
Project description:In this study, we compare genomic signature safter treatment ofprimary human bronchial epithelial cells (HBEC) cultured in 3D with polycyclic aromatic hydrocarbons (PAHs) and identify genesets predictive of cancer risk.
2020-10-28 | GSE156147 | GEO
Project description:Oil spills have polluted the marine environment for decades and continue to be a major source of polycyclic aromatic hydrocarbons (PAHs) to marine ecosystems around the globe. Although the toxicity of PAHs to fish has been well studied, the combined effects of extreme abiotic factors and oil are poorly understood. Gulf of Mexico killifish Fundulus grandis larvae (< 24 hours post hatch) were exposed to varying environmental conditions (dissolved oxygen 2, 6 ppm; temperature 20, 25, 30°C; and salinity 3, 10, 30 ppt) combined with varying concentrations of high energy water accommodated fractions (HEWAF) (total PAHs 0 – ~ 125 ppb) for a total of 48 h. Larvae survival and development were negatively affected by PAHs, starting with the lowest concentration tested (~15 ppb). High temperature + hypoxia + PAHs resulted in the lowest survival with salinity having little impact on any of the endpoints tested. Expression of the hepatic detoxifying gene cyp1a was highly induced in PAH-exposed larvae, but only under normoxic conditions. A lack of cyp1a induction under hypoxia and PAH exposure could explain the enhanced toxicity observed. This work highlights the need for more studies examining the combined impact of suboptimal water quality parameters in the presence of pollution in fish early life-stages.
2019-04-18 | GSE129998 | GEO
Project description:Effects of polycyclic aromatic hydrocarbons on osteoclasts and osteoblasts in the scales of zebrafish
| PRJNA676042 | ENA
Project description:Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally-dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at a concentration that induces developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burden was analyzed at these time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the smallest number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure and may provide a path for unraveling the toxicity of complex PAH mixtures.
2013-05-15 | GSE44130 | GEO
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a mixture of 8 PAHs, benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(ghi)perylene, benzo(k)fluoranthene, chrysene, dibenz(ah)anthracene, and indeno(123,cd)pyrene. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the mixture of 8 PAHs or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
2017-01-01 | GSE87689 | GEO
Project description:Cytochrome P450 enzymes play an important role in bioactivating or detoxifying polycyclic aromatic hydrocarbons (PAHs). We exposed mice to doses of benzo[a]pyrene (BaP) or a mixture of PAHs to characterize dose- and time-response relationships of specific cytochrome P450s. Mice exposed to the highest PAH exposures exhibited 1.7-5-fold higher intrinsic clearance rates for BaP, compared to controls, and higher Vmax values, indicating higher amounts of enzymes capable of metabolizing BaP. This study demonstrates that PAHs induce enzymes in dose- and time-dependent patterns in animal models at exposure levels researchers use to characterize hazards and at relevant human exposure levels to PAH mixtures found at Superfund sites. Accounting for these potential changes in enzyme profiles, relative rates of PAH bioactivation and detoxification, and resulting risk will help reduce uncertainty and improve risk assessments for PAHs at contaminated sites.
2022-10-13 | PXD019472 | Pride
Project description:Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally-dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at a concentration that induces developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burden was analyzed at these time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the smallest number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure and may provide a path for unraveling the toxicity of complex PAH mixtures. Gene expression was measured in zebrafish embryos after exposure to PAHs. Embryos were batch-exposed in groups of 40 to 25 μM BAA, 25 μM DBT, 25 μM PYR or 1% DMSO vehicle control starting at 6 hpf and collected at 24 or 48 hpf. Four independent biological replicates were prepared for each treatment. The reference was a pool of zebrafish embryos exposed to DMSO control until 24 and 48 hpf.
2013-05-15 | E-GEOD-44130 | biostudies-arrayexpress
Project description:To gain deeper insight into the mechanism of toxicity, it is important to identify and characterize miRNAs profiles involved in responses to specific classes of toxicants in conjunction with their impact on gene expression levels. However, few reports have described the effects of toxicants on miRNA expression profiles. Taking into account the prominent role of miRNAs in cancer development, progression, cell cycle control, and proliferation-related processes, it is likely that miRNAs are involved in the toxic response induced by carcinogens. Polycyclic aromatic hydrocarbons (PAHs) are a well-characterized class of human carcinogens. In the present study, we documented the different expression profiles of miRNAs in environmental carcinogen-exposed HepG2 cells by miRNA microarray analysis. To evaluate the change in miRNA expression levels, human hepatocellular carcinoma (HepG2) cells were exposed to two PAHs (benzo[a]anthracene, benzo[k]fluoranthene) for 48 h. miRNA expression analysis was conducted using a 8x16k human miRNA microarray (Agilent Technologies, USA).
2013-07-22 | E-GEOD-49068 | biostudies-arrayexpress