HepG2 treated with Polycyclic Aromatic Hydrocarbons (PAHs)
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ABSTRACT: 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.
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).
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.
Project description:While powerful techniques exist to accurately account for anharmonicity in vibrational molecular spectroscopy, they are computationally very expensive and cannot be routinely employed for large species and/or at non-zero vibrational temperatures. Motivated by the study of Polycyclic Aromatic Hydrocarbon (PAH) emission in space, we developed a new code, which takes into account all modes and can describe all infrared transitions including bands becoming active due to resonances as well as overtone, combination, and difference bands. In this article, we describe the methodology that was implemented and discuss how the main difficulties were overcome, so as to keep the problem tractable. Benchmarking with high-level calculations was performed on a small molecule. We carried out specific convergence tests on two prototypical PAHs, pyrene (C16H10) and coronene (C24H12), aiming at optimising tunable parameters to achieve both acceptable accuracy and computational costs for this class of molecules. We then report the results obtained at 0 K for pyrene and coronene, comparing the calculated spectra with available experimental data. The theoretical band positions were found to be significantly improved compared to harmonic density functional theory calculations. The band intensities are in reasonable agreement with experiments, the main limitation being the accuracy of the underlying calculations of the quartic force field. This is a first step toward calculating moderately high-temperature spectra of PAHs and other similarly rigid molecules using Monte Carlo sampling.
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).
Project description:Polycyclic aromatic hydrocarbon (PAH) contamination in the U.S. Great Lakes has long been of concern, but information regarding the current sources, distribution, and fate of PAH contamination is lacking, and very little information exists for the potentially more toxic nitro-derivatives of PAHs (NPAHs). This study uses fugacity, food web, and Monte Carlo models to examine 16 PAHs and five NPAHs in Lake Michigan, and to derive PAH and NPAH emission estimates. Good agreement was found between predicted and measured PAH concentrations in air, but concentrations in water and sediment were generally under-predicted, possibly due to incorrect parameter estimates for degradation rates, discharges to water, or inputs from tributaries. The food web model matched measurements of heavier PAHs (≥5 rings) in lake trout, but lighter PAHs (≤4 rings) were overpredicted, possibly due to overestimates of metabolic half-lives or gut/gill absorption efficiencies. Derived PAH emission rates peaked in the 1950s, and rates now approach those in the mid-19th century. The derived emission rates far exceed those in the source inventories, suggesting the need to reconcile differences and reduce uncertainties. Although additional measurements and physiochemical data are needed to reduce uncertainties and for validation purposes, the models illustrate the behavior of PAHs and NPAHs in Lake Michigan, and they provide useful and potentially diagnostic estimates of emission rates.
Project description:The regioselective C-H arylation of substituted polycyclic aromatic hydrocarbons (PAHs) is a desired but challenging task. A copper-catalyzed C7-H arylation of 1-naphthamides has been developed by using aryliodonium salts as arylating reagents. This protocol does not need to use precious metal catalysts and tolerates wide variety of functional groups. Under standard conditions, the remote C-H arylation of other PAHs including phenanthrene-9-carboxamide, pyrene-1-carboxamide and fluoranthene-3-carboxamide has also accomplished, which provides an opportunity for the development of diverse organic optoelectronic materials.
Project description:Every year, Northern Thailand faces haze pollution during the haze episode. The particulate matter (PM), including fine fraction (PM2.5), a coarse fraction (PM2.5-10), and 16 polycyclic aromatic hydrocarbons (PAHs), was measured in six provinces in upper north Thailand during the haze and non-haze episodes in 2018. Eighty-three percent of the PM2.5 measurements (21.8-194.0 µg/m3) during the haze episode exceeded the national ambient air quality standard in Thailand. All 16 PAHs were detected in the study area in both periods. The average concentration of total PAHs (particle-bound and gas-phase) during the haze episode was 134.7 ± 80.4 ng/m3, which was about 26 times higher than those in the non-haze (5.1 ± 9.7 µg/m3). Naphthalene and acenaphthene were the dominant PAHs in the gas phase; whereas, indeno[123-cd] pyrene, benzo[a]pyrene, and Benzo[ghi]Perylene were dominant in the particle-bound phase. The estimated inhalation excess cancer risk from PAHs exposure was 9.3 × 10-4 and 2.5 × 10-5 in the haze episode and non-haze, respectively. Diagnostic ratios and principal component analysis revealed that PAHs were derived from mixed sources of vehicle emission and solid combustion in the haze episode and vehicle emission in the non-haze period. High pollution levels of PM and large cancer risk attributable to the exposure of PAHs in the haze episode suggest urgent countermeasures to reduce the source emission, especially from the solid combustion in the area.
Project description:The cycling and fate of polycyclic aromatic hydrocarbons (PAHs) is not well understood in estuarine systems. It is critical now more than ever given the increased ecosystem pressures on these critical coastal habitats. A budget of PAHs and cycling has been created for Galveston Bay (Texas) in the northwestern Gulf of Mexico, an estuary surrounded by 30-50% of the US capacity of oil refineries and chemical industry. We estimate that approximately 3 to 4 mt per year of pyrogenic PAHs are introduced to Galveston Bay via gaseous exchange from the atmosphere (ca. 2 mt/year) in addition to numerous spills of petrogenic PAHs from oil and gas operations (ca. 1.0 to 1.9 mt/year). PAHs are cycled through and stored in the biota, and ca. 20 to 30% of the total (0.8 to 1.5 mt per year) are estimated to be buried in the sediments. Oysters concentrate PAHs to levels above their surroundings (water and sediments) and contain substantially greater concentrations than other fish catch (shrimp, blue crabs and fin fish). Smaller organisms (infaunal invertebrates, phytoplankton and zooplankton) might also retain a significant fraction of the total, but direct evidence for this is lacking. The amount of PAHs delivered to humans in seafood, based on reported landings, is trivially small compared to the total inputs, sediment accumulation and other possible fates (metabolic remineralization, export in tides, etc.), which remain poorly known. The generally higher concentrations in biota from Galveston Bay compared to other coastal habitats can be attributed to both intermittent spills of gas and oil and the bay's close proximity to high production of pyrogenic PAHs within the urban industrial complex of the city of Houston as well as periodic flood events that transport PAHs from land surfaces to the Bay.
Project description:The reaction pathways from phenyl radicals to phenanthrene (A3) and pyrene (A4) via C2H3 and C4H4 additions were investigated using the G3(MP2, CC) method. Rate constants of elementary reactions were calculated. The influence of additions, H-abstraction ways and reactive sites on the reaction rates were considered. These polycyclic aromatic hydrocarbon (PAH) formation pathways were used to improve the combustion chemistry model for C4 fuels, and the results from the improved model and the original model were compared with experimental data. H atoms are important for PAH formation owing to their influential roles in the production of aromatic radicals and stable aromatic structures. C2H3 and C4H4 addition reactions can occur at low temperature, and need less energy than C2H2 addition. The PAH formation pathways determined from G3 calculations, which were used to improve the model, were effective in promoting PAH formations in this model. Comparison of PAH formation in butane and butadiene flames showed both the C2H3 and C4H4 addition pathways included in this work can improve the formation of PAHs in butadiene and butane flames. C4H4 addition pathways in a butane flame were better for PAH formation than C2H3 addition.