Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE267217 | GEO | 2024/08/05
REPOSITORIES: GEO
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Project description:BackgroundDiesel exhaust particles (DEP), which contain hazardous compounds, are emitted during the combustion of diesel. As approximately one-third of the vehicles worldwide use diesel, there are growing concerns about the risks posed by DEP to human health. Long-term exposure to DEP is associated with airway hyperresponsiveness, pulmonary fibrosis, and inflammation; however, the molecular mechanisms behind the effects of DEP on the respiratory tract are poorly understood. Such mechanisms can be addressed by examining transcriptional and DNA methylation changes. Although several studies have focused on the effects of short-term DEP exposure on gene expression, research on the transcriptional effects and genome-wide DNA methylation changes caused by long-term DEP exposure is lacking. Hence, in this study, we investigated transcriptional and DNA methylation changes in human adenocarcinoma alveolar basal epithelial A549 cells caused by prolonged exposure to DEP and determined whether these changes are concordant.ResultsDNA methylation analysis using the Illumina Infinium MethylationEPIC BeadChips showed that the methylation levels of DEP-affected CpG sites in A549 cells changed in a dose-dependent manner; the extent of change increased with increasing dose reaching the statistical significance only in samples exposed to 30 µg/ml DEP. Four-week exposure to 30 µg/ml of DEP significantly induced DNA hypomethylation at 24,464 CpG sites, which were significantly enriched for DNase hypersensitive sites, genomic regions marked by H3K4me1 and H3K27ac, and several transcription factor binding sites. In contrast, 9,436 CpG sites with increased DNA methylation levels were significantly overrepresented in genomic regions marked by H3K27me3 as well as H3K4me1 and H3K27ac. In parallel, gene expression profiling by RNA sequencing demonstrated that long-term exposure to DEP altered the expression levels of 2,410 genes, enriching 16 gene sets including Xenobiotic metabolism, Inflammatory response, and Senescence. In silico analysis revealed that the expression levels of 854 genes correlated with the methylation levels of the DEP-affected cis-CpG sites.ConclusionsTo our knowledge, this is the first report of genome-wide transcriptional and DNA methylation changes and their associations in A549 cells following long-term exposure to DEP.
| S-EPMC11299313 | biostudies-literature
Project description:Our aim was to test the hypothesis that exposure to whole diesel exhaust (WDE) would enhance angiogenesis/vasculogenesis. Male apolipoprotein E-deficient mice, with either scaffold implantation subcutaneously or hindlimb ischemia, were exposed to either WDE (containing diesel exhaust particle [DEP] at a concentration of about 1mg/m(3)) or filtered air 6 h/day, 5 days/week in a whole body exposure chamber for 2, 5, or 8 weeks, respectively. WDE exposure significantly increased total cell counts in the scaffolds, aortic, and perivascular fat tissues. Macrophage infiltration was enhanced and CD31 expression increased in the scaffolds, which was coupled by increased alpha-smooth muscle actin (alpha-SMA) expression. WDE exposure led to increased CD31 expression, while decreasing endothelial nitric oxide synthase in the aortic wall. The vessel volume measured by micro-CT was increased in ischemic and non-ischemic hindlimbs in response to WDE exposure. DEP exposure induced capillary-like tube formation in endothelial cells in vitro, and caused capillary sprouting from aortic rings ex vivo. In addition, WDE exposure significantly increased mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, while decreasing prolylhydroxylase (PHD) 2 expression. WDE exposure increases inflammatory cell infiltration, enhances the vessel volume/flow, and increases capillary tube formation and sprouting, thereby inducing angiogenesis and vasculogenesis. The angiogenic effects may occur through increasing HIF-1alpha and VEGF while decreasing PHD2 expression.
| S-EPMC2784267 | biostudies-literature
Project description:Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells
| PRJNA1110253 | ENA
Project description:The vast majority of neurodegenerative disease cannot be attributed to genetic causes alone and as a result, there is significant interest in identifying environmental modifiers of disease risk. Epidemiological studies have supported an association between long-term exposure to air pollutants and disease risk. Here, we investigate the mechanisms by which diesel exhaust, a major component of air pollution, induces neurotoxicity. Using a zebrafish model, we found that exposure to diesel exhaust particulate extract caused behavioral deficits and a significant decrease in neuron number. The neurotoxicity was due, at least in part, to reduced autophagic flux, which is a major pathway implicated in neurodegeneration. This neuron loss occurred alongside an increase in aggregation-prone neuronal protein. Additionally, the neurotoxicity induced by diesel exhaust particulate extract in zebrafish was mitigated by co-treatment with the autophagy-inducing drug nilotinib. This study links environmental exposure to altered proteostasis in an in vivo model system. These results shed light on why long-term exposure to traffic-related air pollution increases neurodegenerative disease risk and open up new avenues for exploring therapies to mitigate environmental exposures and promote neuroprotection.
| S-EPMC7357183 | biostudies-literature
Project description:We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 ?M), 1-NP (1 and 10 ?M) and 3-NBA (0.5 and 5 ?M). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH) nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.
| S-EPMC5037673 | biostudies-literature
Project description:Human BEAS-2B bronchial epithelial cells were exposed directly at the air-liquid interphase towards exhaust gas and particles of a ship engine. The goal was to compare the responses towards different fuel combustions. The engine run either on diesel fuel (DF) or on Heavy Fuel Oil (HFO). The lung cells were exposed 3 times to each combustion aerosol (DF or HFO). The duration of the exposure was 4h. The cells were seeded into transwell-inserts 24h before exposure. Within each exposure 3 transwell-inserts were exposed to the complete aerosol and 3 transwell-inserts were exposed to the filtered aerosol. Effects of the complete aerosol were referenced against the filtered aerosol to determine the effects of the aerosol particles.
2015-02-01 | E-GEOD-63962 | biostudies-arrayexpress
Project description:BackgroundRecent epidemiological studies indicate early-life exposure to pollution particulate is associated with adverse neurodevelopmental outcomes. The need is arising to evaluate the risks conferred by individual components and sources of air pollution to provide a framework for the regulation of the most relevant components for public health protection. Previous studies in rodent models have shown diesel particulate matter has neurotoxic potential and could be a health concern for neurodevelopment. The present study shows an evaluation of pathological and protracted behavioral alterations following neonatal exposure to aerosolized diesel exhaust particles (NIST SRM 1650b). The particular behavioral focus was on temporal control learning, a broad and fundamental cognitive domain in which reward delivery is contingent on a fixed interval schedule. For this purpose, C57BL/6?J mice were exposed to aerosolized NIST SRM 1650b, a well-characterized diesel particulate material, from postnatal days 4-7 and 10-13, for four hours per day. Pathological features, including glial fibrillary-acidic protein, myelin basic protein expression in the corpus callosum, and ventriculomegaly, as well as learning alterations were measured to determine the extent to which NIST SRM 1650b would induce developmental neurotoxicity.ResultsTwenty-four hours following exposure significant increases in glial-fibrillary acidic protein (GFAP) in the corpus callosum and cortex of exposed male mice were present. Additionally, the body weights of juvenile and early adult diesel particle exposed males were lower than controls, although the difference was not statistically significant. No treatment-related differences in males or females on overall locomotor activity or temporal learning during adulthood were observed in response to diesel particulate exposure.ConclusionWhile some sex and regional-specific pathological alterations in GFAP immunoreactivity suggestive of an inflammatory reaction to SRM 1650b were observed, the lack of protracted behavioral and pathological deficits suggests further clarity is needed on the developmental effects of diesel emissions prior to enacting regulatory guidelines.
| S-EPMC6322252 | biostudies-literature
Project description:Human BEAS-2B bronchial epithelial cells were exposed directly at the air-liquid interphase towards exhaust gas and particles of a ship engine. The goal was to compare the responses towards different fuel combustions. The engine run either on diesel fuel (DF) or on Heavy Fuel Oil (HFO).
2015-02-01 | GSE63962 | GEO
Project description:Diesel engine exhaust (DEE) is a predominant contributor to urban air pollution. The International Agency for Research on Cancer classified DEE as a group I carcinogen. Inflammatory response is considered to be associated with various health outcomes including carcinogenesis. However, human data linking inflammation with long-term DEE exposure are still lacking. In this study, a total of 137 diesel engine testing workers with an average exposure of 8.2 years and 108 unexposed controls were enrolled. Peripheral blood samples were collected from all subjects, and the association of DEE exposure with inflammatory biomarkers was analyzed. Overall, DEE exposed workers had a significant increase in the C-reactive protein (CRP) and a significant decrease in cytokines including interleukin (IL)-1β, IL-6, IL-8, and macrophage inflammatory protein (MIP)-1β compared to controls after adjusting for age, BMI, smoking status, and alcohol use, and findings were highly consistent when stratified by smoking status. In addition, exposure time dependent patterns for IL-6 and CRP were also found (Ptrend = 0.006 and 0.026, respectively); however, the levels of IL-1β and MIP-1β were significantly lower in subjects with a DEE working time of less than 10 years compared with the controls and then recovered to control levels in workers exposed for >10 years. There were no significant differences in blood cell counts and major lymphocyte subsets between exposed workers and the controls. Our results provide epidemiological evidence for the relationship between DEE exposure and immunotoxicity considering the important roles of cytokines in immunological processes.
| S-EPMC6060680 | biostudies-literature
Project description:BACKGROUND:Short-term controlled exposure to diesel exhaust (DE) in chamber studies have shown mixed results on lung and systemic effects. There is a paucity of studies on well-characterized real-life DE exposure in humans. In the present study, 29 healthy volunteers were exposed to DE while sitting as passengers in diesel-powered trains. Exposure in electric trains was used as control scenario. Each train scenario consisted of three consecutive days (6?h/day) ending with biomarker samplings. RESULTS:Combustion-derived air pollutants were considerably higher in the passenger carriages of diesel trains compared with electric trains. The concentrations of black carbon and ultrafine particles were 8.5??g/m3 and 1.2-1.8?×?105 particles/cm3 higher, respectively, in diesel as compared to electric trains. Net increases of NOx and NO2 concentrations were 317??g/m3 and 36??g/m3. Exposure to DE was associated with reduced lung function and increased levels of DNA strand breaks in peripheral blood mononuclear cells (PBMCs), whereas there were unaltered levels of oxidatively damaged DNA, soluble cell adhesion molecules, acute phase proteins in blood and urinary excretion of metabolites of polycyclic aromatic hydrocarbons. Also the microvascular function was unaltered. An increase in the low frequency of heart rate variability measures was observed, whereas time-domain measures were unaltered. CONCLUSION:Exposure to DE inside diesel-powered trains for 3?days was associated with reduced lung function and systemic effects in terms of altered heart rate variability and increased levels of DNA strand breaks in PBMCs compared with electric trains. TRIAL REGISTRATION:ClinicalTrials.Gov ( NCT03104387 ). Registered on March 23rd 2017.
| S-EPMC6558821 | biostudies-literature