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In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.

ABSTRACT: Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72?h to 5- and 50-?g/ml doses of the water soluble extract of 6 types of PM: soil dust, road dust, agricultural dust, traffic exhausts, biomass burning, and pollen, collected in January-April of 2014 in the area of Little Rock, Arkansas. Cytotoxicity, oxidative potential, epigenetic endpoints, and chromosomal aberrations were addressed. Exposure to 6 types of PM resulted in induction of cytotoxicity and oxidative stress in a type-, time-, and dose-dependent manner. Epigenetic alterations were characterized by type-, time-, and dose-dependent decreases of DNA methylation/demethylation machinery, increased DNA methyltransferases enzymatic activity and protein levels, and transcriptional activation and subsequent silencing of transposable elements LINE-1, SINE B1/B2. The most pronounced changes were observed after exposure to soil dust that were also characterized by hypomethylation and reactivation of satellite DNA and structural chromosomal aberrations in the exposed cells. The results of our study indicate that the water-soluble fractions of the various types of PM have differential potential to target the cellular epigenome.

SUBMITTER: Miousse IR

PROVIDER: S-EPMC5009441 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.

Miousse Isabelle R IR Chalbot Marie-Cecile G MC Pathak Rupak R Lu Xiaoyan X Nzabarushimana Etienne E Krager Kimberly K Aykin-Burns Nukhet N Hauer-Jensen Martin M Demokritou Philip P Kavouras Ilias G IG Kavouras Ilias G IG Koturbash Igor I

Toxicological sciences : an official journal of the Society of Toxicology 20150904 2

Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-μg/ml doses of the water soluble extract of 6 type ...[more]

PMID: 26342214

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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression

Project description:Epidemiological and toxicological studies have suggested that the health effects associated with exposure to particulate matter (PM) are related to the different physicochemical properties of PM. These effects occur through the initiation of differential cellular responses including: the induction of antioxidant defenses, proinflammatory responses, and ultimately cell death. The main objective of this study was to investigate the effects of size-fractionated ambient PM on epithelial cells in relation to their physicochemical properties. Concentrated ambient PM was collected on filters for three size fractions: coarse (aerodynamic diameter [AD] 2.5-10 μm), fine (0.15-2.5 μm), and quasi-ultrafine (<0.2 μm), near a busy street in Toronto, Ontario, Canada. Filters were extracted and analyzed for chemical composition and redox activity. Chemical analyses showed that the coarse, fine, and quasi-ultrafine particles were comprised primarily of metals, water-soluble species, and organic compounds, respectively. The highest redox activity was observed for fine PM. After exposure of A549 cells to PM (10-100 μg/ml) for 4 h, activation of antioxidant, proinflammatory and cytotoxic responses were assessed by determining the expression of heme oxygenase (HMOX-1, mRNA), interleukin-8 (IL-8, mRNA), and metabolic activity of the cells, respectively. All three size fractions induced mass-dependent antioxidant, proinflammatory, and cytotoxic responses to different degrees. Quasi-ultrafine PM caused significant induction of HMOX-1 at the lowest exposure dose. Correlation analyses with chemical components suggested that the biological responses correlated mainly with transition metals and organic compounds for coarse and fine PM and with organic compounds for quasi-ultrafine PM. Overall, the observed biological responses appeared to be related to the combined effects of size and chemical composition and thus both of these physicochemical properties should be considered when explaining PM toxicity.

Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness; Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 Âµm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) âinduced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naÃ¯ve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Experiment Overall Design: animals were treated by PBS, Oval albumin, PM, or both OVA/PM

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In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.

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In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.

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