benzo(a)pyrene
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The aim of the study was to analyze the variables that modify the levels of oxidative DNA damage and lipid peroxidation in non-smoking mothers and their newborns from environmentally distinct localities of the Czech Republic: Ceske Budejovice (CB, an agricultural region) and Karvina (an industrial region). Personal, socio-economic and medical data, concentrations of particulate matter of aerodynamic diameter < 2.5 μm (PM2.5) and benzo[a]pyrene (B[a]P) in the ambient air, the activities of antioxidant mechanisms (superoxide dismutase, catalase, glutathione peroxidase) and antioxidant capacity), the levels of pro-inflammatory cytokines, the concentrations of persistent organic pollutants (POPs) in blood plasma/cord blood plasma and urinary levels of polycyclic aromatic hydrocarbons metabolites (OH-PAHs) were investigated as parameters potentially affecting the markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG) and lipid peroxidation (15-F2t-isoprostane, 15-F2t-IsoP). Significantly higher levels of POPs were detected in the plasma of mothers/newborns from CB (p < 0.001), while increased external levels of B[a]P and PM2.5, confirmed by analyzing urinary OH-PAHs, were found in Karvina subjects (p < 0.001). In mothers, multivariate analysis showed no significant difference in oxidative stress markers (15-F2t-IsoP, 8-oxodG) between the two localities. The analysis further revealed that neither in CB nor, unexpectedly, in Karvina, did PAH exposure affect maternal lipid peroxidation. Significant associations between OH-PAHs and 15-F2t-IsoP or 8-oxodG were observed only in newborns. In addition, multivariate analyses revealed a borderline significant association between locality and 8-oxodG in the urine of all newborns (p = 0.05). In conclusion, not only the maternal exposure of PAHs but also some POPs can negatively affect oxidative stress status in the early-life of newborns.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Telomere length is a biomarker of cellular aging, influenced by various environmental and lifestyle factors. Air pollution is a known environmental stressor that may impact telomere dynamics. This study aimed to investigate the effect of age, lifetime exposure to air pollution, inflammatory parameters and selected lifestyle factors on telomere length. METHODS: The study included 356 participants aged 35-65 living in two regions with varying pollution. Telomere length was measured using qPCR. Individual lifetime exposures to PM10, PM2.5, NO2, benzo(a)pyrene and benzene were calculated based on historical air quality data. Statistical analysis of age, pollution exposure, inflammatory parameters, and lifestyle factors on telomere length was performed using logistic regression and generalized linear models, with odds ratios calculated. RESULTS: Unexpectedly, higher air pollutants lifetime exposures were associated with longer telomeres, particularly for PM10 51-55 μg/m3 (OR = 5.67, p < 0.001), PM2.5 42-45 μg/m3 (OR = 6.56, p < 0.001), B(a)P 6.9-8.3 ng/m3 (OR = 5.25, p = 0.002), NO2 26-27 μg/m3 (OR = 5.22, p = 0.001) and benzene 2.45-2.75 μg/m3 (OR = 6.13, p < 0.001). Age significantly affected telomere length, with older individuals having shorter telomeres. Socioeconomic factors such as college education were positively associated with longer telomeres, while lifestyle factors did not show significant associations. IL-8 was identified as a significant inflammatory marker negatively associated with very long telomeres. CONCLUSION: These baseline findings bring new perspective to the relationship between air pollution and telomere length. Contrary to traditional views, the results suggest potential adaptive responses, highlighting the need for further longitudinal research to explore telomere dynamics over time in conjunction with other factors.
- MeSH
- benzen analýza škodlivé účinky MeSH
- benzopyren analýza MeSH
- dospělí MeSH
- homeostáza telomer * MeSH
- kohortové studie MeSH
- látky znečišťující vzduch * analýza škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxid dusičitý analýza MeSH
- pevné částice analýza škodlivé účinky MeSH
- senioři MeSH
- telomery * účinky léků MeSH
- vystavení vlivu životního prostředí * analýza škodlivé účinky MeSH
- životní styl MeSH
- znečištění ovzduší * škodlivé účinky analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Persons living in industrial environments are exposed to levels of air pollution that can affect their health and fertility. The Czech capital city, Prague, and the Ostrava industrial agglomeration differ in their major sources of air pollution. In Prague, heavy traffic produces high levels of nitrogen oxides throughout the year. In the Ostrava region, an iron industry and local heating are sources of particulate matter (PM) and benzo[a]pyrene (B[a]P), especially in the winter. We evaluated the effects of air pollution on human sperm mitochondrial DNA (mtDNA). Using real-time PCR, we analysed sperm mtDNA copy number and deletion rate in Prague city policemen in two seasons (spring and autumn) and compared the results with those from Ostrava. In Prague, the sperm mtDNA deletion rate was significantly higher in autumn than in spring, which is the opposite of the results from Ostrava. The sperm mtDNA copy number did not show any seasonal differences in either of the cities; it was correlated negatively with sperm concentration, motility, and viability, and with sperm chromatin integrity (assessed with the Sperm Chromatin Structure Assay). The comparison between the two cities showed that the sperm mtDNA deletion rate in spring and the sperm mtDNA copy number in autumn were significantly lower in Prague vs. Ostrava. Our study supports the hypothesis that sperm mtDNA deletion rate is affected by the composition of air pollution. Sperm mtDNA abundance is closely associated with chromatin damage and standard semen characteristics.
- MeSH
- dospělí MeSH
- látky znečišťující vzduch toxicita škodlivé účinky MeSH
- lidé MeSH
- mitochondriální DNA * genetika MeSH
- motilita spermií účinky léků MeSH
- pevné částice toxicita škodlivé účinky MeSH
- policie MeSH
- roční období MeSH
- spermie * účinky léků MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- znečištění ovzduší * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFβ1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.
- MeSH
- benzopyren * toxicita MeSH
- epitelové buňky * metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- poškození DNA MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Environmental exposure is associated with increased incidence of respiratory and cardiovascular diseases and reduced fertility. Exposure to air pollution can influence gene expression through epigenetic mechanisms. In this study, we analysed gene-specific CpG methylation in spermatozoa of city policemen occupationally exposed to air pollution in two Czech cities differing by sources and composition of the air pollution. In Prague, the pollution is mainly formed by NO2 from heavy traffic. Ostrava is a hotspot of industrial air pollution with high concentrations of particular matter (PM) and benzo[a]pyrene (B[a]P). We performed genome-wide methylation sequencing using the SureSelectXT Human Methyl-Seq system (Agilent Technologies) and next-generation sequencing to reveal differentially methylated CpG sites and regions. We identified differential methylation in the region chr5:662169 - 663376 annotated to genes CEP72 and TPPP. The region was then analysed in sperm DNA from 117 policemen using targeted methylation sequencing, which proved its hypermethylation in sperm of Ostrava policemen.
- MeSH
- dospělí MeSH
- látky znečišťující vzduch * analýza toxicita MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * účinky léků MeSH
- pevné částice analýza toxicita MeSH
- policie MeSH
- pracovní expozice MeSH
- spermie * účinky léků MeSH
- znečištění ovzduší * škodlivé účinky analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
DNA damage can impair normal cellular functions and result in various pathophysiological processes including cardiovascular diseases and cancer. We compared the genotoxic potential of diverse DNA damaging agents, and focused on their effects on the DNA damage response (DDR) and cell fate in human lung cells BEAS-2B. Polycyclic aromatic hydrocarbons [PAHs; benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP)] induced DNA strand breaks and oxidative damage to DNA; anticancer drugs doxorubicin (DOX) and 5-bromo-2'-deoxyuridine (BrdU) were less effective. DOX triggered the most robust p53 signaling indicating activation of DDR, followed by cell cycle arrest in the G2/M phase, induction of apoptosis and senescence, possibly due to the severe and irreparable DNA lesions. BrdU not only activated p53, but also increased the percentage of G1-phased cells and caused a massive accumulation of senescent cells. In contrast, regardless the activation of p53, both PAHs did not substantially affect the cell cycle distribution or senescence. Finally, a small fraction of cells accumulated only in the G2/M phase and exhibited increased cell death after the prolonged incubation with B[a]P. Overall, we characterized differential responses to diverse DNA damaging agents resulting in specific cell fate and highlighted the key role of DNA lesion type and the p53 signaling persistence.
BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project. METHODS: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI). RESULTS: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP μg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk. CONCLUSIONS: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens. IMPACT: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures.
- MeSH
- karcinogeny MeSH
- lidé MeSH
- nádory plic * chemicky indukované epidemiologie MeSH
- plíce MeSH
- polycyklické aromatické uhlovodíky * škodlivé účinky MeSH
- pracovní expozice * škodlivé účinky analýza MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
The testis is a priority organ for developing alternative models to assess male reproductive health hazards of chemicals. This study characterized a 3D in vitro model of murine prepubertal Leydig TM3 cells with improved expression of steroidogenesis markers suitable for image-based screening of testicular toxicity. This 3D scaffold-free spheroid model was applied to explore the impact of prototypical endocrine-disrupting chemicals (EDCs) and environmental reprotoxicants (benzo[a]pyrene, 2- and 9-methylanthracenes, fluoranthene, triclosan, triclocarban, methoxychlor) on male reproductive health. The results were compared to the male reprotoxicity potential of EDCs assessed in a traditional monolayer (2D) culture. The testicular toxicity was dependent not only on the type of culture (2D vs. 3D models) but also on the duration of exposure. Benzo[a]pyrene and triclocarban were the most active compounds, eliciting cytotoxic effects in prepubertal Leydig cells at low micromolar concentrations, which might be a mechanism contributing to their male reprotoxicity.
- MeSH
- benzopyren toxicita MeSH
- endokrinní disruptory * chemie MeSH
- Leydigovy buňky * MeSH
- myši MeSH
- rozmnožování MeSH
- testis MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Byla studována nemocnost 300 dětí od narození do 2 let v okresech Karviná (KI) a České Budějovice (CB), lišících se stupněm znečištění ovzduší. Podle očekávání byly více nemocné děti v okrese Karviná, nejčastější byly infekce horních cest dýchacích, onemocnělo 84 % dětí z KI a 75 % dětí z CB, s průměrnou frekvencí 126,8 diagnóz / 100 dětí / rok v KI oproti 98 diagnózám / 100 dětí / rok v CB. Onemocnění dolních cest dýchacích byla srovnatelná v obou okresech, za celé sledované období onemocnělo 29,7 % dětí v KI a 30,7 % dětí v CB, s frekvencí 26,85 dg / 100 dětí / rok v KI a 24,6 dg / 100 dětí / rok v CB. Vyšší nemocnost v Karviné byla také u virových onemocnění, nemocí gastrointestinálního traktu a kůže.
The morbidity of 300 children from birth to 2 years in the districts of Karviná (KI) and České Budějovice (CB), differing in the degree of air pollution, was studied. As expected, there were more sick children in the Karviná district, the most common being upper respiratory tract infections, with an average frequency of 126,8 dg / 100 children / year compared to 98 dg / 100 children / year in CB. 84% of children from KI and 75% of children from CB became ill. The proportion of children with lower respiratory tract disease was comparable – 29.7% in KI and 30.7% in CB, with a frequency of 26.85 dg / 100 children in KI and 24.6 dg / 100 children in CB. Higher morbidity in Karviná was also in viral diseases, diseases of the gastrointestinal tract and skin. Key words: children aged 0–2 years, morbidity, air pollution, benzo(a)pyrene
- MeSH
- kojenec MeSH
- lidé MeSH
- morbidita * MeSH
- nemoci dýchací soustavy MeSH
- novorozenec MeSH
- výzkum MeSH
- znečištění ovzduší * MeSH
- znečištění životního prostředí MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The aim of this work was to estimate the share of selected significant risk factors for respiratory cancer in the overall incidence of this disease and their comparison in two environmentally different burdened regions. A combination of a longitudinal cross-sectional population study with a US EPA health risk assessment methodology was used. The result of this procedure is the expression of lifelong carcinogenic risks and their contribution in the overall incidence of the disease. Compared to exposures to benzo[a]pyrene in the air and fibrogenic dust in the working air, several orders of magnitude higher share of the total incidence of respiratory cancer was found in radon exposures, for women 60% in the industrial area, respectively 100% in the non-industrial area, for men 24%, respectively 15%. The share of risks in workers exposed to fibrogenic dust was found to be 0.35% in the industrial area. For benzo[a]pyrene, the share of risks was below 1% and the share of other risk factors was in the monitored areas was up to 85%. The most significant share in the development of respiratory cancer in both monitored areas is represented by radon for women and other risk factors for men.
- MeSH
- hodnocení rizik MeSH
- inhalační expozice * statistika a číselné údaje MeSH
- karcinogeny MeSH
- lidé MeSH
- prach MeSH
- pracovní expozice * statistika a číselné údaje MeSH
- průmysl MeSH
- průřezové studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
