BACKGROUND: Asthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes - T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) - warrants clarification. OBJECTIVES: To explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype). METHODS: In a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma-overweight/obese (OV/OB) combined outcomes. RESULTS: The non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9-11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7-428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG. CONCLUSIONS: Ambient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.
- MeSH
- 8-hydroxy-2'-deoxyguanosin moč MeSH
- benzopyren analýza MeSH
- bronchiální astma krev epidemiologie patofyziologie moč MeSH
- dinoprost analogy a deriváty krev MeSH
- dítě MeSH
- fenotyp MeSH
- kojenec MeSH
- kotinin moč MeSH
- látky znečišťující vzduch analýza MeSH
- lidé MeSH
- mladiství MeSH
- plíce patofyziologie MeSH
- předškolní dítě MeSH
- studie případů a kontrol MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS: Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS: The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS: The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.
- MeSH
- antigen CTLA-4 genetika MeSH
- benzopyren analýza MeSH
- bronchiální astma chemicky indukované genetika MeSH
- cytochrom P-450 CYP2E1 genetika MeSH
- dítě MeSH
- genetická predispozice k nemoci * MeSH
- genotyp MeSH
- interakce genů a prostředí MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- městské obyvatelstvo MeSH
- studie případů a kontrol MeSH
- transkripční faktor STAT4 genetika MeSH
- venkovské obyvatelstvo MeSH
- vystavení vlivu životního prostředí analýza MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- znečištění ovzduší analýza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
This article is directed to determining concentrations of polycyclic aromatic hydrocarbons (PAHs), which are sorbed to solid particles in the air. Pollution sources were identified on the basis of the ratio of benzo[ghi]perylene (BghiPe) to benzo[a]pyrene (BaP). Because various important information is lost by determining the simple ratio of concentrations, least squares linear regression (classic ordinary least squares regression), reduced major axis, orthogonal regression, and Kendall-Theil robust diagnostics were utilized for identification. Statistical evaluation using all aforementioned methods demonstrated different ratios of the monitored PAHs in the intervals examined during warmer and colder periods. Analogous outputs were provided by comparing gradients of the emission factors acquired from the measured concentrations of BghiPe and BaP in motor vehicle exhaust gases. Based on these outputs, it was possible plausibly to state that the influence of burning organic fuels in heating stoves is prevalent in colder periods whereas in warmer periods transport was the exclusive source because other sources of PAH emissions were not found in the examined locations.
- MeSH
- benzopyren analýza MeSH
- hodnocení rizik MeSH
- látky znečišťující vzduch analýza MeSH
- lineární modely MeSH
- metoda nejmenších čtverců MeSH
- monitorování životního prostředí metody statistika a číselné údaje MeSH
- perylen analogy a deriváty analýza MeSH
- pevné částice analýza MeSH
- polycyklické aromatické uhlovodíky analýza MeSH
- roční období MeSH
- urbanizace MeSH
- výfukové emise vozidel analýza MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
This study estimated current benzo(a)pyrene (BaP) concentration levels, population exposure and potential health impacts of exposure to ambient air BaP in Europe. These estimates were done by combining the best available information from observations and chemical transport models through the use of spatial interpolation methods. Results show large exceedances of the European target value for BaP in 2012 over large areas, particularly in central-eastern Europe. Results also show large uncertainties in the concentration estimates in regions with a few or no measurement stations. The estimation of the population exposure to BaP concentrations and its health impacts was limited to 60% of the European population, covering only the modelled areas which met the data quality requirement for modelling of BaP concentrations set by the European directive 2004/107/EC. The population exposure estimate shows that 20% of the European population is exposed to BaP background ambient concentrations above the EU target value and only 7% live in areas with concentrations under the estimated acceptable risk level of 0.12 ng m(-3). This exposure leads to an estimated 370 lung cancer incidences per year, for the 60% of the European population included in the estimation. Emissions of BaP have increased in the last decade with the increase in emissions from household combustion of biomass. At the same time, climate mitigation policies are promoting the use of biomass burning for domestic heating. The current study shows that there is a need for more BaP measurements in areas of low measurement density, particularly where high concentrations are expected, e.g. in Romania, Bulgaria, and other Balkan states. Furthermore, this study shows that the health risk posed by PAH exposure calls for better coordination between air quality and climate mitigation policies in Europe.
- MeSH
- benzopyren * škodlivé účinky analýza MeSH
- biomasa MeSH
- incidence MeSH
- látky znečišťující vzduch * škodlivé účinky analýza MeSH
- lidé MeSH
- nádory plic epidemiologie etiologie MeSH
- rizikové faktory MeSH
- vystavení vlivu životního prostředí * škodlivé účinky analýza MeSH
- vytápění MeSH
- znečištění ovzduší * škodlivé účinky analýza MeSH
- znečištění vzduchu ve vnitřním prostředí škodlivé účinky analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
- východní Evropa epidemiologie MeSH
The Northern Moravia Region is the most polluted region in the Czech Republic by particulate matter (PM2.5) and carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as benzo[a]pyrene (B[a]P) by heavy industry and local heating. This specific situation was used to study the impact of air pollution on newborns in the exposed Karviná district and control district of České Budějovice. Biological material from newborns and mothers was collected in summer and winter seasons. This project is highly detailed, analyzing the concentrations of PAHs in ambient air and diet, in human breast milk, in the urine of mothers and newborns, using biomarkers of genetic damage as DNA adducts and gene expression analysis, biomarkers of oxidative stress as 8-oxodG adducts and lipid peroxidation (15-F2t-isoprostane immunoassay). All 400 children, for whom the biomarker data at delivery were obtained, will be followed for morbidity up to 2 years of age. The Northern Moravia Region seems to be to be a model area for studying the long-term impact of human health exposure to c-PAHs. Our observations will indicate possible genetic and oxidative damage in newborns, which may significantly affect their morbidity.
- MeSH
- adukty DNA MeSH
- benzopyren analýza MeSH
- deoxyguanosin analogy a deriváty analýza MeSH
- dieta MeSH
- dospělí MeSH
- genom * MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- látky znečišťující vzduch analýza MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- monitorování životního prostředí MeSH
- novorozenec MeSH
- oxidační stres MeSH
- pevné částice analýza MeSH
- polycyklické aromatické uhlovodíky analýza MeSH
- průmysl MeSH
- roční období MeSH
- těhotenství MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- benzopyren analýza MeSH
- financování organizované MeSH
- interpretace statistických dat MeSH
- látky znečišťující vzduch analýza MeSH
- longitudinální studie MeSH
- oxid dusnatý analýza MeSH
- oxid siřičitý analýza MeSH
- oxid uhelnatý analýza MeSH
- ozon analýza MeSH
- prach analýza MeSH
- statistika jako téma MeSH
- znečištění ovzduší analýza MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
A surface plasmon resonance (SPR) biosensor for simultaneous detection of multiple organic pollutants exhibiting endocrine-disrupting activity, namely atrazine, benzo[a]pyrene, 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-nonylphenol, is reported. The biosensor utilizes a multichannel SPR sensor based on wavelength modulation of SPR and wavelength division multiplexing (WDM) of sensing channels, antibodies as biorecognition element and a competitive immunoassay detection format. An analysis time of 45 min (including 30-min incubation of the sample with antibodies) and limits of detection as low as 0.05, 0.07, 0.16 and 0.26 ng mL(-1) are demonstrated for benzo[a]pyrene, atrazine, 2,4-D and 4-nonylphenol, respectively. The biosensor is also shown to be regenerable and suitable for repeated use.
- MeSH
- atrazin analýza MeSH
- benzopyren analýza MeSH
- biosenzitivní techniky metody přístrojové vybavení MeSH
- časové faktory MeSH
- endokrinní disruptory analýza MeSH
- fenoly analýza MeSH
- financování organizované MeSH
- imunoanalýza metody MeSH
- kyselina 2,4-dichlorfenoxyoctová analýza MeSH
- povrchová plasmonová rezonance metody přístrojové vybavení MeSH
- senzitivita a specificita MeSH
The effect of exposure to organic compounds adsorbed onto respirable air particles (<2.5microm) on DNA adducts in lymphocytes was studied in a group of non-smoking policemen (N=109, aged 35+/-0.9 years) working in the downtown area of Prague and spending >8h daily outdoors. Personal exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed on respirable particles was monitored in each subject for 48h before biological sampling. DNA adducts were analyzed by a (32)P-postlabelling assay, and total DNA adduct levels and B[a]P-like spots were determined. Further biomarkers included cotinine levels in urine to control for exposure to tobacco smoke, plasma levels of vitamins A, E and C and polymorphisms of metabolic genotypes (GSTM1, GSTP1, GSTT1, CYP 1A1-Msp I and Ile/Val, MTHFR, MS), DNA repair genotypes (XRCC1, hOGG1 and XPD exons 6 and 23) and the p53 gene (p53 Msp I and BstU I). All the biomarkers of exposure and effect were analyzed repeatedly during a period of one year at 2-3 month intervals (January, March, June, September 2004) to cover periods with high (winter) and low (summer) levels of air pollution. The highest personal exposure to c-PAHs was found in January (8.1+/-8.8ng/m(3)), while the other three sampling periods exhibited 3-4-fold lower c-PAH exposure. The total DNA adducts were only slightly elevated in January (2.08+/-1.60) compared to March (1.66+/-0.65), June (1.96+/-1.73) and September (1.77+/-1.77). B[a]P-like DNA adducts, however, were significantly higher in January than in the March and June sampling periods (0.26+/-0.14 vs. 0.19+/-0.12 and 0.22+/-0.13, respectively; p<0.0001 and p=0.017) indicating that c-PAH exposure probably plays a crucial role in DNA adduct formation in lymphocytes. No effect of individual metabololic or DNA repair genotypes on DNA adduct levels was observed. However, the combination of two genotypes encoding enzymes metabolizing c-PAHs - CYP 1A1 and GSTM1 - was associated with the levels of total and B[a]P-like DNA adducts under conditions of increased exposure to c-PAHs. Our study suggests that DNA adducts in the lymphocytes of subjects exposed to increased c-PAH levels are an appropriate biomarker of a biologically effective dose, directly indicating whether or not the extent of exposure to these compounds is related to an increased mutagenic and carcinogenic risk.
- MeSH
- adukty DNA analýza MeSH
- benzopyren analýza toxicita MeSH
- biologické markery analýza MeSH
- dospělí MeSH
- financování organizované MeSH
- genotyp MeSH
- karcinogeny životního prostředí analýza toxicita MeSH
- látky znečišťující vzduch v pracovním prostředí analýza toxicita MeSH
- látky znečišťující vzduch analýza toxicita MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty chemie účinky léků MeSH
- mutageny analýza toxicita MeSH
- pracovní expozice MeSH
- znečištění ovzduší analýza škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
The impact of air pollution exposure on the level of total DNA adducts in human white blood cells (WBCs) was evaluated in two populations in the Czech Republic and compared to the exposure-DNA adduct relationship in other populations in the US and China in human lung cells and rodent lung tissue. The human populations examined were exposed to respirable particles (< 2.5 microm) (PM2.5) in urban, rural, and occupational settings where the particles originated from coal and petroleum fuel combustion, coke production, and other coal-tar aerosols (e.g., used in aluminum production). These particles contain carcinogenic polycyclic aromatic hydrocarbons (PAHs) that are known to form DNA adducts through covalent binding. Personal exposure to PM2.5 and PAHs were measured prior to collection of blood samples for DNA adduct analysis by 32P-postlabeling. Coke oven workers (n = 76), in 10 job categories on the top and side of a coke oven in Ostrava, CZ, were studied and compared to a different population exposed to environmental levels of PAHs from air pollution in Teplice, CZ. Personal exposures to airborne particles ranged from < 1 to more than 15,000 microg/m3 and carcinogenic PAHs exposure ranged from < 5 to > 200,000 ng/m3. At low to moderate environmental exposures to carcinogenic PAHs, DNA adduct levels in the WBCs were significantly correlated with exposure. However, at the higher occupational levels found on the coke oven, the exposure-DNA adduct relationship became non-linear. Under these high exposure conditions, the relative DNA adduct level per unit of exposure (DNA-binding potency) was significantly lower than measured at environmental exposures. This finding is consistent with observations in lung cells from bronchoalveolar lavage of humans exposed to a wide range of PAH. This same high exposure-dose non-linearity was also observed in lung DNA from rats exposed by inhalation to a coal-tar pitch aerosol. DNA adduct levels in all these cases show evidence of a form of non-linearity at high doses that has been described by Lutz (W.K. Lutz, Dose-response relationship and low dose extrapolation in chemical carcinogenesis, Carcinogenesis, 11 (1990) 1243-1247) as a superlinear dose response. This superlinear response may be due to saturation of metabolic activation enzymes, induction of either DNA repair processes or detoxification enzymes, or other mechanisms. Regardless of the mechanism, this decrease in the DNA-binding potency at moderate to high doses of PAH has important implications for dose-response extrapolation in risk assessment.
- MeSH
- adukty DNA krev MeSH
- benzopyren analýza toxicita MeSH
- dehet uhelný škodlivé účinky MeSH
- endonukleasy metabolismus MeSH
- karcinogeny škodlivé účinky MeSH
- kouření MeSH
- krysa rodu rattus MeSH
- látky znečišťující vzduch v pracovním prostředí škodlivé účinky MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- leukocyty chemie MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- polycyklické aromatické uhlovodíky škodlivé účinky MeSH
- potkani Wistar MeSH
- pracovní expozice MeSH
- radioizotopy fosforu metabolismus MeSH
- vystavení vlivu životního prostředí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH