Reduced gene expression levels after chronic exposure to high concentrations of air pollutants

Rössner, Pavel; Tulupova, Elena; Rössnerová, Andrea; Líbalová, Helena; Hoňková, K.; Gmuender, Hans; Pastorková, Anna; Švecová, Vlasta; Topinka, Jan; Šrám, Radìm J.

doi:10.1016/j.mrfmmm.2015.08.001

Cited by 31 publications

(12 citation statements)

References 55 publications

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“…Our previous studies showed differences in DNA methylation patterns between locations differing significantly in air pollution levels, and confirmed our previous data on gene expression profiles Sram et al, 2013;Rossner et al, 2015). The results of our multivariate logistic regression analysis of the newborns' samples showed 8-oxodG levels were more probable to be affected by selected variables in combination with mothers' personal PM2.5 and B[a]P exposure than 15-F2t-IsoP levels.…”

Section: Discussionsupporting

confidence: 90%

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Ambroz

Vlkova

Rössner

et al. 2016

International Journal of Hygiene and Environmental Health

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Ambient air particulate matter (PM) represents a class of heterogeneous substances that form one component of air pollution. Oxidative stress has been implicated as an important action mechanism for PM on the human organism. Oxidative damage induced by reactive oxygen species (ROS) may affect any cellular macromolecule. The aim of our study was to investigate the impact of air pollution on oxidative DNA damage [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)] and lipid peroxidation [15-F2t-isoprostane (15-F2t-IsoP)] in the urine and blood from mothers and newborns from two localities with different levels of air pollution: Ceske Budejovice (CB), a locality with a clean air, and Karvina, a locality with high air pollution. The samples from normal deliveries (38-41 week+) of nonsmoking mothers and their newborns were collected in the summer and winter seasons. Higher PM2.5 concentrations were found in Karvina than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62μg/m(3), P<0.001), and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34μg/m(3), P<0.001). We observed significant differences in 15-F2t-IsoP levels between the summer and winter seasons in Karvina for newborns (mean±SD: 64.24±26.75 vs. 104.26±38.18pg/ml plasma, respectively) (P<0.001). Levels of 8-oxodG differed only in the winter season between localities, they were significantly higher (P<0.001) in newborns from Karvina in comparison with CB (mean±SD: 5.70±2.94 vs. 4.23±1.51 nmol/mmol creatinine, respectively). The results of multivariate regression analysis in newborns from Karvina showed PM2.5 concentrations to be a significant predictor for 8-oxodG excretion, PM2.5 and B[a]P (benzo[a]pyrene) concentrations to be a significant predictor for 15-F2t-IsoP levels. The results of multivariate regression analysis in mothers showed PM2.5 concentrations to be a significant predictor of 8-oxodG levels.

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Section: Discussionsupporting

confidence: 90%

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Ambroz

Vlkova

Rössner

et al. 2016

International Journal of Hygiene and Environmental Health

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“…Both experimental and observational studies demonstrate the capacity of NO 2 along with other air pollutants to activate oxidant pathways through formation of ROS, triggering inflammation and cell death (Lodovici and Bigagli 2011). Studies in human bronchial epithelial cells showed differential expression of genes involved in response to oxidative stress following air pollution exposure (Rossner et al 2015; Zhou et al 2015). In our study we observed differential methylation in CAT and TPO .…”

Section: Discussionmentioning

confidence: 99%

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO ₂ Air Pollution Exposure

Gruzieva

Breton

et al. 2017

Environ Health Perspect

201

142

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Background:Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.Objectives:We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.Methods:We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).Results:We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.Conclusions:NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.Citation:Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104–110; http://dx.doi.org/10.1289/EHP36

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“…Rossner et al (2015) reported deregulation of expression of respiratory chain, oxidative phosphorylation, and mitochondrial membrane pathways when comparing gene expression profiles in adult nonsmoking men from a heavily polluted area versus a control region in the Czech Republic across different seasons (winter and summer 2009 and winter 2010).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

Vrijens

Winckelmans

Tsamou

et al. 2017

Environ Health Perspect

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Background:Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.Objectives:Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.Methods:Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant’s residential address using spatiotemporal interpolation in combination with a dispersion model.Results:Average long-term PM10 was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m3 in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).Conclusions:Expression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.Citation:Vrijens K, Winckelmans E, Tsamou M, Baeyens W, De Boever P, Jennen D, de Kok TM, Den Hond E, Lefebvre W, Plusquin M, Reynders H, Schoeters G, Van Larebeke N, Vanpoucke C, Kleinjans J, Nawrot TS. 2017. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women. Environ Health Perspect 125:660–669; http://dx.doi.org/10.1289/EHP370

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Reduced gene expression levels after chronic exposure to high concentrations of air pollutants

Cited by 31 publications

References 55 publications

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO ₂ Air Pollution Exposure

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

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Reduced gene expression levels after chronic exposure to high concentrations of air pollutants

Cited by 31 publications

References 55 publications

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO 2 Air Pollution Exposure

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

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Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO ₂ Air Pollution Exposure