Publications by authors named "Radim J Sram"

136 Publications

Airborne Benzo[a]Pyrene may contribute to divergent Pheno-Endotypes in children.

Environ Health 2021 Apr 9;20(1):40. Epub 2021 Apr 9.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.

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-F-isoprostane (15-F-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/m) compared to that in the non-atopic controls (3.83 ng/m; 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/m, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m; 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-F-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-F-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.
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http://dx.doi.org/10.1186/s12940-021-00711-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035778PMC
April 2021

The effects of age on DNA fragmentation, the condensation of chromatin and conventional semen parameters in healthy nonsmoking men exposed to traffic air pollution.

Health Sci Rep 2021 Jun 9;4(2):e260. Epub 2021 Mar 9.

Department of Genetic Toxicology and Epigenetics Institute of Experimental Medicine, Czech Academy of Science Prague Czech Republic.

Background: Numerous studies have investigated age-based declines in semen traits, but the impact of paternal age on semen parameter values remains inconclusive.

Objectives: The aim of this study was to detect an impact of age on semen quality was studied in healthy nonsmoking men exposed to traffic air pollution.

Methods: Semen samples from 150 Prague City policemen aged 23 to 63 years were examined for standard semen parameters, sperm DNA fragmentation and high DNA stainability.

Results: A significant positive correlation was found between age and %DFI ( = .359,  < .001), and negative correlations were found between age and sperm vitality ( = -.247,  < .001), the % acrosome-intact sperm ( = -.202, = .013) and the % normal sperm heads ( = -.204, = .012). A weak but significant negative correlation was found for high DNA stainability (% HDS) vs age ( = -.161, = .050). No significant correlation was detected between male age and the other investigated semen quality parameters. At ages of 23 to 30, 31 to 40, 41 to 50, and 51 to 63 years, the mean %DFI values were 12.7 ± 7.18, 14.7 ± 7.42, 19.6 ± 11.25, and 34.2 ± 15.08, respectively.

Conclusion: Our study shows a strong relationship ( < .001) between the age of men and sperm DNA fragmentation in an occupational cohort at risk of exposure to heavy traffic-related air pollution in a large city center.
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http://dx.doi.org/10.1002/hsr2.260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942397PMC
June 2021

The impact of air pollution to obesity.

Neuro Endocrinol Lett 2020 Sep;41(3):146-153

Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine, AS CR, Prague, Czech Republic.

Backgroud: Air pollution in ambient air could affect the increase of obesity in children.

Method: Review analyze papers about the effect of polycyclic aromatic hydrocarbons (PAHs), fine particles (particulate matter < 2.5 μm, PM2.5), and traffic air pollution (NO2, NOx, PM2.5).

Results: Prenatal exposure to concentrations 1.73-3.07 ng/m3 PAHs significantly increased obesity at age 5 and 7 years, up to 11 years. All studies indicate the significance of prenatal exposure with concentration > 0.3 ng/m3 of B[a]P (benzo[a]pyrene). Prenatal exposure to PM2.5 above concentrations 10.6-11.9 μg/m3 increased obesity in children up to the age of 9 years. Traffic air pollution was evaluated according to exposure to NO2 and PM2.5. Concentrations NO2 higher 30 μg/m3 affect adiponectin levels in cord blood, cholesterol metabolism, and therefore increase later the risk of overweight or obesity. PM2.5 9.2-11.6 μg/m3 during pregnancy affect adiponectin. These concentrations from the traffic air pollution can affect the metabolism in newborns later related to obesity.

Conclusion: All these studies indicate that contemporary concentrations of PAHs, PM2.5 and NO2 in ambient air, especially during prenatal period, affect overweight and obesity in children.
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September 2020

The Impact of Cesarean and Vaginal Delivery on Results of Psychological Cognitive Test in 5 Year Old Children.

Medicina (Kaunas) 2020 Oct 21;56(10). Epub 2020 Oct 21.

Faculty of Health and Social Sciences, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic.

The impact of cesarean and vaginal delivery on cognitive development was analyzed in 5 year old children. : Two cohorts of 5 year old children born in the years 2013 and 2014 in Karvina (Northern Moravia) and Ceske Budejovice (Southern Bohemia) were studied for their cognitive development related to vaginal ( = 117) and cesarean types of delivery ( = 51). The Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used as psychological tests. : In the comparison of vaginal delivery vs. cesarean section, the children delivered by cesarean section scored lower and, therefore, achieved poorer performance in cognitive tests compared to those born by vaginal delivery, as shown in the RCPM ( < 0.001) and in the BG test ( < 0.001). When mothers' education level was considered, the children whose mothers achieved a university degree scored higher in both the RCPM test ( < 0.001) and the BG test ( < 0.01) compared to the children of mothers with lower secondary education. When comparing mothers with a university degree to those with higher secondary education, there was a significant correlation between level of education and score achieved in the RCPM test ( < 0.001), but not in the BG test. : According to our findings, the mode of delivery seems to have a significant influence on performance in psychological cognitive tests in 5 year old children in favor of those who were born by vaginal delivery. Since cesarean-born children scored notably below vaginally born children, it appears possible that cesarean delivery may have a convincingly adverse effect on children's further cognitive development.
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http://dx.doi.org/10.3390/medicina56100554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589839PMC
October 2020

Effect of Polycyclic Aromatic Hydrocarbons Exposure on Cognitive Development in 5 Years Old Children.

Brain Sci 2020 Sep 7;10(9). Epub 2020 Sep 7.

Faculty of Health and Social Sciences, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic.

To analyze the impact of polycyclic aromatic hydrocarbons (PAHs) in ambient air at the time of delivery and five years of age on cognitive development in five year old children. Two cohorts of children born in the years 2013 and 2014 from Karvina (Northern Moravia, = 70) and Ceske Budejovice (Southern Bohemia, = 99) were studied at the age of five years for their cognitive development related to the exposure to PAHs, determined in the ambient air as the concentration of benzo[a]pyrene (B[a]P) and OH-PAH (hydroxy-PAH) metabolites in urine of the newborns at the time of delivery. As psychological tests, the Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used. Concentrations of B[a]P in the third trimester of mother's pregnancies were 6.1 ± 4.53 ng/m in Karvina, and 1.19 ± 1.28 ng/m ( < 0.001) in Ceske Budejovice. Neither the outcome of the RCPM test nor the BG test differed between children in Karvina vs. Ceske Budejovice, or boys vs. girls. Cognitive development in five year old children was affected by the higher exposure to PM2.5 during the third trimester in girls in Karvina. We did not observe any significant effect of prenatal PAH exposure on psychological cognitive tests in five year old children.
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http://dx.doi.org/10.3390/brainsci10090619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563279PMC
September 2020

Impact of Air Pollution on the Health of the Population in Parts of the Czech Republic.

Authors:
Radim J Sram

Int J Environ Res Public Health 2020 09 4;17(18). Epub 2020 Sep 4.

Faculty of Health and Social Science, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic.

Thirty years ago, Northern Bohemia in the Czech Republic was one of the most air polluted areas in Europe. After political changes, the Czech government put forward a research program to determine if air pollution is really affecting human health. This program, later called the "Teplice Program", was initiated in collaboration with scientists from the United States Environmental Protection Agency (US EPA). This cooperation made possible the use of methods on the contemporary level. The very high concentrations of sulphur dioxide (SO), particulate matter of 10 micrometers or less (PM10), and polycyclic aromatic hydrocarbons (PAHs) present in the air showed, for the first time, the impact of air pollutants on the health of the population in mining districts: adverse pregnancy outcomes, the impact of air pollution on sperm morphology, learning disabilities in children, and respiratory morbidity in preschool children. A surprising result came from the distribution of the sources of pollution: 70% of PM10 pollution came from local heating and not from power plants as expected. Thanks to this result, the Czech government supported changes in local heating from brown coal to natural gas. This change substantially decreased SO and PM10 pollution and affected mortality, especially cardiovascular mortality.
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http://dx.doi.org/10.3390/ijerph17186454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558327PMC
September 2020

Challenge-comet assay, a functional and genomic biomarker for precision risk assessment and disease prevention among exposed workers.

Toxicol Appl Pharmacol 2020 Apr 17;397:115011. Epub 2020 Apr 17.

University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania; University of Texas Medical Branch, Galveston, TX, USA. Electronic address:

Advancements in genomic technologies have ushered application of innovative changes into biomedical sciences and clinical medicine. Consequently, these changes have created enormous opportunities to implement precision population/occupational disease prevention and target-specific disease intervention (or personalized medicine). To capture the opportunities, however, it is necessary is to develop novel, especially genomic-based, biomarkers which can provide precise and individualized health risk assessment. In this review, development of the Challenge-comet assay is used as an example to demonstrate how assays need to be validated for its sensitivity, specificity, and functional and quantitative features, and how assays can be used to provide individualized health risk assessment for precision prevention and intervention. Other examples of genomic-based novel biomarkers will also be discussed. Furthermore, no biomarkers can be used alone therefore their integrated usage with other biomarkers and with personal data bases will be discussed.
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http://dx.doi.org/10.1016/j.taap.2020.115011DOI Listing
April 2020

Comparison of polycyclic aromatic hydrocarbon metabolite concentrations in urine of mothers and their newborns.

Sci Total Environ 2020 Jun 21;723:138116. Epub 2020 Mar 21.

University of Chemistry and Technology, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28 Prague, Czech Republic. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants produced during incomplete combustion of organic matter. Humans can be exposed to them via several pathways (inhalation, digestion, dermal exposure). The aim of this study was to assess the concentration of 11 monohydroxylated metabolites of PAHs (OH-PAHs) in 660 urine samples collected from mothers and their newborns residing in two localities of the Czech Republic - Most and Ceske Budejovice - in 2016 and 2017. After enzymatic hydrolysis, the target analytes were extracted from the urine samples using liquid-liquid extraction, with extraction solvent ethyl acetate and a clean-up step using dispersive solid-phase extraction (d-SPE) with the Z-Sep sorbent. For identification and quantification, ultra-high performance liquid chromatography coupled with tandem mass spectrometry was applied. 2-OH-NAP was the compound present in all of the measured samples and it was also the compound at the highest concentration in both mothers' and newborns' urine samples (median concentration 5.15 μg/g creatinine and 3.58 μg/g creatinine). The total concentrations of OH-PAHs in urine samples collected from mothers were 2 times higher compared to their children. The most contaminated samples were collected in Most in the period October 2016-March 2017 from both mothers (12.59 μg/g creatinine) and their newborns (8.29 μg/g creatinine). The concentrations of OH-PAHs in urine samples, which were collected from both mothers and their newborns as presented in this study, are comparable with those found in our previous study between 2013 and 2014. In addition, they are slightly lower or comparable to other studies from Poland, USA, Germany, China, and Australia. The results might indicate that the population in the previously highly air-polluted mining districts carries some long-term changes (maybe existing changes in genetic information), which also affect the metabolism of PAHs. It could be related to the long-lasting effect, and thus corresponding to the shortened life expectancy.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138116DOI Listing
June 2020

Relation between personal exposure and outdoor concentrations of carcinogenic polycyclic aromatic hydrocarbons during smog episode.

Cent Eur J Public Health 2019 12;27(4):305-311

Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic.

Objectives: To our knowledge this is the first study measuring personal exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) bound to airborne particulate matter ≤ 2.5 µm (PM) in periods of high air pollution (smog episode) in which citizen were tracked.

Methods: Measurements were performed in industrial regions of the Czech Republic: Ostrava, Karviná, Havířov. The city of Prague served as a control. Personal monitoring was conducted by active personal monitors for 48 hours. Non-smoking city policemen from Prague, Karviná and Havířov, office workers from Ostrava city and volunteers from Ostrava-Radvanice and Bartovice participated in the study (N = 214).

Results: The average personal exposure to benzo[a]pyrene (B[a]P) was highest in Ostrava (17.2 ng/m), followed by Karviná, Havířov, Radvanice and Bartovice, and Prague (14.2, 12.0, 9.3, and 2.8 ng/m, respectively). We tested for association between the personal exposure to cPAHs and various health-related factors extracted from the questionnaires, including lifestyle factors and day-to-day activities.

Conclusions: Exposure to outdoor cPAHs, environmental tobacco smoke (ETS), commuting, and time spent indoors (in restaurants, workplace or home) were found to be the main determinants of the personal exposure. Daily cPAHs measurements in highly polluted areas are needed for evaluating the personal exposure and to avoid its underestimation resulting from stationary monitoring.
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http://dx.doi.org/10.21101/cejph.a5475DOI Listing
December 2019

Estimation of human exposure to polycyclic aromatic hydrocarbons (PAHs) based on the dietary and outdoor atmospheric monitoring in the Czech Republic.

Environ Res 2020 03 3;182:108977. Epub 2019 Dec 3.

University of Chemistry and Technology, Prague, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28, Prague 6, Czech Republic. Electronic address:

In everyday life, humans can be exposed to various chemicals including ubiquitous polycyclic aromatic hydrocarbons (PAHs) mostly through food consumption and/or inhalation. In the presented study, we evaluated PAH concentrations in duplicate samples (n = 251). Concurrently, the outdoor concentrations of PM2.5-bound PAHs in filters (n = 179) were also monitored. The daily exposure to PAHs was subsequently estimated for the risk group of pregnant women living in two different cities (Most city and Ceske Budejovice city) in the Czech Republic. This is the first unique study in Europe to evaluate human daily exposure to 20 PAHs both from inhalation (outdoor air) and dietary intake. For the analysis of samples collected during the years 2016/2017, a gas chromatography coupled to tandem mass spectrometry was applied. Focusing on the diet samples, a slightly higher sum of detected PAHs was measured in duplicates obtained from the mothers living in the Most city (0.115-186 ng g) compared to the Ceske Budejovice city (0.115-97.1 ng g). This could be due to a higher occurrence of major analytes (pyrene, phenanthrene and fluoranthene) and the different composition of daily diet. The values of toxic and most often detected substance, namely benzo[a]pyrene (BaP), were also higher by 35% in the Most city. Regarding the outdoor air contamination (only particulate phase - PM2.5 was assessed), here the opposite situation was observed, relatively higher amounts of all PAHs were monitored in the Ceske Budejovice city (median: 2.22 ng m) than in the Most city (median: 1.07 ng m). These higher PAH concentrations in the Ceske Budejovice city are probably caused by more intense traffic, higher population and also by the occurrence of old-fashioned heating plant. Depending on a seasonal variability, especially during the cold season, the concentrations of BaP exceeded the European average emission limit (1 ng m) by 1.5-6 times. This highest inhalation exposure to all PAHs was observed in February. However, the dietary intake still represents the dominant contributor (>90%) to the total PAH exposure.
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http://dx.doi.org/10.1016/j.envres.2019.108977DOI Listing
March 2020

Corrigendum to "Benzo[a]pyrene is associated with dysregulated myelo-lymphoid hematopoiesis in asthmatic children" [Environ. Int. 128 (2019) 218-232].

Environ Int 2019 Nov 28;132:105121. Epub 2019 Aug 28.

Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2019.105121DOI Listing
November 2019

Benzo[a]pyrene is associated with dysregulated myelo-lymphoid hematopoiesis in asthmatic children.

Environ Int 2019 07 3;128:218-232. Epub 2019 May 3.

Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Background: The extent to which ambient benzo[a]pyrene (B[a]P) contributes to mechanistically distinct de novo asthma remains unknown.

Objectives: To identify molecular signatures and regulatory networks underlying childhood exposure to ambient B[a]P and asthma, using robust and unbiased systems biology approaches.

Methods: Clinically confirmed asthmatic (n = 191) vs. control (n = 194) children (aged, 7-15) were enrolled from a polluted urban center and semi-rural region in Czech Republic. Contemporaneous B[a]P concentration, gene expressions, DNA methylation data were analyzed against asthma diagnosis, as well as a modified prognostic index of asthma, using integrative multiscale co-expression network analysis. Sample-wise cell type compositions were inferred by a machine learning approach (i.e. CIBERSORT) with reference gene expressions of purified 38 distinct hematopoietic cell states from umbilical cord (i.e. stem cell/progenitors) or peripheral blood (i.e. lymphocytes).

Results: The median outdoor B[a]P was increased near the homes of the urban children with 'moderate' or 'severe' prognostic markers of asthma, but not in the urban controls. An elevated B[a]P induced epigenetic suppression of NF-κB inflammation, decreased Natural Killer T (NKT) cells and activated anti-inflammatory IL10-secreting CD8+ T effective memory cells. B[a]P was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appears to promote concurrent increase of neutrophilic metamyelocyte and mature CD71 erythroid cells. Furthermore, erythroid-specific master transcription regulator gene (GATA1), glutathione transferase genes (GSTM1 and GSTM3) and Eosinophil marker (IL5RA) were simultaneously activated in the urban asthma cases.

Conclusions: B[a]P might contribute to concurrent suppression of pro-inflammatory (e.g. NF-κB mediated NKT cells), and activation of anti-inflammatory pathways (e.g. IL10-secreting CD8+ T cells) in the urban asthmatic children. In addition, B[a]P appears to elevate heme biosynthesis, which in turn, promotes neutrophilic metamyelocyte expansion and reduction of CD71 erythroids.
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http://dx.doi.org/10.1016/j.envint.2019.04.052DOI Listing
July 2019

Urinary metabolites of phthalates and di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH)-Czech mothers' and newborns' exposure biomarkers.

Environ Res 2019 06 30;173:342-348. Epub 2019 Mar 30.

University of Chemistry and Technology, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, Prague 6, 16628, Czech Republic. Electronic address:

To assess human exposure to hazardous diesters of phthalic acid and their substitute di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH), concentrations of their metabolites in urine should be determined. For the purpose of this biomonitoring study, a quick and easy sample preparation procedure for the simultaneous determination of eight phthalate and four DINCH metabolites in urine has been implemented and validated. Following the enzymatic hydrolysis and dilution with methanol, the sample is ready for the analysis by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The limits of quantification of this method ranged from 0.15 to 0.4 ng/mL urine with recoveries of 60-126% and repeatability in the range of 1-11%. The validated method was subsequently used for the analysis of urine samples collected from mothers and their newborn children living in two localities of the Czech Republic (Karvina and Ceske Budejovice, 2013-2014). Median concentrations of all measured metabolites (∑metabolites) were slightly lower in the urine samples collected from children (77.7 ng/mL urine) compared to their mothers (115.3 ng/mL urine), but no correlation was found between the concentrations of target compounds in children's and mothers' urine samples. The analyte with the highest concentration was monobutyl phthalate (MBP), with the median concentration of 32.1 ng/mL urine in the urine samples collected from mothers and 17.2 ng/mL urine in the samples collected from their children. This compound was also found in almost all of the measured samples. On the other hand, mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH) was not found in any urine sample. The most contaminated samples were collected from children living in the Karvina locality (median ∑metabolites 103.2 ng/mL urine), where the mono (2-ethyl-5-carboxypentyl) phthalate (cx-MEHP) compound contributed 43% to the total content of phthalate metabolites in newborns' urine. The results from our study are comparable with concentrations of the target compounds from Norway and Germany and lower compared to the results concluded in Sweden.
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http://dx.doi.org/10.1016/j.envres.2019.03.067DOI Listing
June 2019

Greater susceptibility of girls to airborne Benzo[a]pyrene for obesity-associated childhood asthma.

Environ Int 2018 12 17;121(Pt 1):308-316. Epub 2018 Sep 17.

Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA. Electronic address:

Background: Sexually dimorphic risk of obesity-associated asthma is posited to accelerate around puberty. Yet, the role of air pollution on the lean and obese asthmatic children has never been examined.

Objective: To compare whether a unit exposure to airborne benzo[a]pyrene (B[a]P) is associated with altered risks of asthma across the overweight/obese (OV/OB) control, lean asthmatic, and OV/OB asthmatic children, respectively, compared to the lean controls, before and after adjusting for oxidant stress markers (i.e. 15‑F2t‑IsoP, 8‑oxo‑dG, and Carbonyl).

Methods: Asthmatic and healthy control children, recruited from polluted urban and rural areas, were matched to ambient concentration of B[a]P. A unit increase in B[a]P and multinomial logistic regression on OV/OB control, lean asthmatic, and OV/OB asthma were compared across the sex- and age-groups.

Results: The median B[a]P was associated with a linear increase among the female children, according to OV/OB and asthma, respectively, and together, compared to the lean control girls (p = 0.001). While B[a]P was associated with positive relationship with 15‑F2t‑IsoP level among the OV/OB boys, the same exposure-outcome association was inverse among the OV/OB girls. One natural log-unit increase in ambient B[a]P was associated with 10.5-times greater odds (95% CI, 2.6-39.6; p = 0.001) the adolescent OV/OB boys, compared to the unit odds among the lean controls. In contrast, the adolescent OV/OB girls were associated with highest adjusted odds of the asthma (aOR = 15.4; 95% CI, 2.9-29.1; p < 0.001) compared to the lean control girls. An adjustment for 15‑F2t‑IsoP, and Carbonyls was associated with greater odds of asthma per unit exposure for the adolescent OV/OB girls (aOR = 16.2; 95% CI, 1.4-181.8; p = 0.024).

Conclusions: B[a]P exposure was associated with a leap in the odds of asthma among the OV/OB adolescents, particularly the girls, after adjusting for 15‑F2t‑IsoP and Carbonyls.
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http://dx.doi.org/10.1016/j.envint.2018.08.061DOI Listing
December 2018

Gene expression profiling in healthy newborns from diverse localities of the Czech Republic.

Environ Mol Mutagen 2018 06 30;59(5):401-415. Epub 2018 Mar 30.

Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

Prenatal exposure to air pollution is associated with intrauterine growth restriction and low birth weight. Gene expression changes in newborns in relation to air pollution have not been sufficiently studied. We analyzed whole genome expression in cord blood leukocytes of 202 newborns from diverse localities of the Czech Republic, differing among other factors in levels of air pollution: the district of Karvina (characterized by higher concentration of air pollutants) and Ceske Budejovice (lower air pollution levels). We aimed to identify differentially expressed genes (DEGs) and pathways in relation to locality and concentration of air pollutants. We applied the linear model to identify the specific DEGs and the correlation analysis, to investigate the relationship between the concentrations of air pollutants and gene expression data. An analysis of biochemical pathways and gene set enrichment was also performed. In general, we observed modest changes of gene expression, mostly attributed to the effect of the locality. The highest number of DEGs was found in samples from the district of Karvina. A pathway analysis revealed a deregulation of processes associated with cell growth, apoptosis or cellular homeostasis, immune response-related processes or oxidative stress response. The association between concentrations of air pollutants and gene expression changes was weak, particularly for samples collected in Karvina. In summary, as we did not find a direct effect of exposure to air pollutants, we assume that the general differences in the environment, rather than actual concentrations of individual pollutants, represent a key factor affecting gene expression changes at delivery. Environ. Mol. Mutagen. 59:401-415, 2018. © 2018 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/em.22184DOI Listing
June 2018

Modeling Unobserved Heterogeneity in Susceptibility to Ambient Benzo[a]pyrene Concentration among Children with Allergic Asthma Using an Unsupervised Learning Algorithm.

Int J Environ Res Public Health 2018 01 10;15(1). Epub 2018 Jan 10.

Departments of Environmental Health Sciences, Epidemiology, and Biostatistics State University of New York at Albany School of Public Health, Rensselaer, NY 12144, USA.

Current studies of gene × air pollution interaction typically seek to identify unknown heritability of common complex illnesses arising from variability in the host's susceptibility to environmental pollutants of interest. Accordingly, a single component generalized linear models are often used to model the risk posed by an environmental exposure variable of interest in relation to a priori determined DNA variants. However, reducing the phenotypic heterogeneity may further optimize such approach, primarily represented by the modeled DNA variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also identify single nucleotide polymorphisms (SNP) associated with phenotype subgroups. Specifically, we first apply an unsupervised learning algorithm method and a non-parametric regression to find a biclustering structure of children according to their allergy and asthma severity. We then identify a set of SNPs most closely correlated with each sub-group. We subsequently fit a logistic regression model for each group against the healthy controls using benzo[]pyrene (B[]P) as a representative airborne carcinogen. Application of such approach in a case-control data set shows that SNP clustering may help to partly explain heterogeneity in children's asthma susceptibility in relation to ambient B[]P concentration with greater efficiency.
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http://dx.doi.org/10.3390/ijerph15010106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800205PMC
January 2018

The impact of air pollution to central nervous system in children and adults.

Neuro Endocrinol Lett 2017 Dec;38(6):389-396

Faculty of Health and Social Studies, South Bohemian University, Ceske Budejovice, Czech Republic.

The aim of this paper was to review studies analyzing the associations between air pollution and neurodevelopment in children as well as the effect on adult population. Effect of prenatal exposure to polycyclic aromatic hydrocarbons (PAHs, benzo[a]pyrene, B[a]P) were already studied on cohorts from New York, Poland, China, and Spain. All results indicate changes of child behavior and neurodevelopment at the age of 3-9 years, decrease of IQ, increase of Attention Deficit Hyperactivity Disorder (ADHD), decrease of brain-derived neurotrophic factor (BDNF), reduction of left hemisphere white matter. Effect of traffic-related air pollution (TRAP) to neurobehavioral development in children, measured as PM2.5 (particulate matter <2.5 µm), PM10, elemental carbon (EC), black smoke (BC), NO2, NOx, were studied in USA, Spain, Italy, and South Korea. Increased concentrations of TRAP were associated with the increase of ADHD, autism, affected cognitive development; PM2.5 decreased the expression of BDNF in placenta. Increased concentrations of PM2.5 affected adults cognition (episodic memory), increased major depressive disorders. Increased concentrations of NO2 were associated with dementia, NOx with Parkinson's disease. Increased concentrations of PAHs, PM2.5 and NO2 in polluted air significantly affect central nervous system in children and adults and represent a significant risk factor for human health.
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December 2017

Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms.

Mutat Res 2017 07 12;773:188-203. Epub 2017 Jul 12.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic. Electronic address:

The human population is continually exposed to numerous harmful environmental stressors, causing negative health effects and/or deregulation of biomarker levels. However, studies reporting no or even positive impacts of some stressors on humans are also sometimes published. The main aim of this review is to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution (benzo[a]pyrene) and radiation (uranium, X-ray examination and natural radon background), on the differently exposed population groups. Because some results obtained from cytogenetic studies were opposite than hypothesized, we have searched for a meaningful interpretation in genomic/epigenetic studies. A detailed analysis of our data supported by the studies of others and current epigenetic knowledge, leads to a hypothesis of the versatile mechanism of adaptation to environmental stressors via DNA methylation settings which may even originate in prenatal development, and help to reduce the resulting DNA damage levels. This hypothesis is fully in agreement with unexpected data from our studies (e.g. lower levels of DNA damage in subjects from highly polluted regions than in controls or in subjects exposed repeatedly to a pollutant than in those without previous exposure), and is also supported by differences in DNA methylation patterns in groups from regions with various levels of pollution. In light of the adaptation hypothesis, the following points may be suggested for future research: (i) the chronic and acute exposure of study subjects should be distinguished; (ii) the exposure history should be mapped including place of residence during the life and prenatal development; (iii) changes of epigenetic markers should be monitored over time. In summary, investigation of human adaptation to the environment, one of the most important processes of survival, is a new challenge for future research in the field of human biomonitoring that may change our view on the results of biomarker analyses and potential negative health impacts of the environment.
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http://dx.doi.org/10.1016/j.mrrev.2017.07.002DOI Listing
July 2017

Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms.

Environ Pollut 2017 Dec 12;231(Pt 1):1134-1144. Epub 2017 Aug 12.

Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address:

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/m) 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.
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http://dx.doi.org/10.1016/j.envpol.2017.07.057DOI Listing
December 2017

Oxidative stress in newborns by different modes of delivery.

Neuro Endocrinol Lett 2016 Nov;37(6):445-451

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Objectives: The aim of our study is to investigate the impact of the type of delivery - vaginal vs. cesarean section on oxidative damage determined as the lipid peroxidation (15-F2t-isoprostane (15-F2t-IsoP) in the cord blood of newborns and venous blood from mothers in 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.

Resutls: In Karvina, the concentration of PM2.5 was higher than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62 µg/m3, p<0.001) and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34 µg/m3, p<0.001). Similarly, the concentration of B[a]P was higher in Karvina than in CB in the summer 2013 (mean±SD: 1.16±0.91 vs. 0.16±0.26 ng/m3, p<0.001) and in the winter 2014 (5.36±3.64 vs. 1.45±1.19 ng/m3, p<0.001). Delivery procedures differed by the type of anesthesia; at the Cesarean section in CB was used general anesthesia in 73.8% vs. 20.8% in Karvina (p<0.001), epidural anesthesia in CB in 26.2% vs. 77.1% in Karvina (p<0.001), at vaginal delivery was local anesthesia used in CB in 58.9% vs. 14.1% in Karvina (p<0.001). In CB was oxidative stress higher after vaginal delivery (101.7±31.0 pg 15-F2t-isoP/ml plasma) vs. Cesarean section (83.9±26.9 pg 15-F2t-isoP/ml plasma, p<0.001), no difference between the type of delivery was observed in Karvina.

Conclusion: No difference between the types of delivery was observed in mothers in CB as well as in Karvina. Oxidative stress in newborns in Karvina was significantly affected by the concentrations of PM2.5 and B[a]P in the polluted air.
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November 2016

The impact of air pollution in the Southern Bohemia Region on fetuses and newborns.

Neuro Endocrinol Lett 2016 Dec;37(suppl 2):52-57

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Department of Genetic Ecotoxicology, Prague, Czech Republic.

Air pollution with increased concentrations of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs, represented by benzo[a]pyrene, B[a]P) affect fetal development, reduce birth weights (LBW) of newborns, and increases intrauterine growth retardation (IUGR). The Southern Bohemia Region is believed to be one of the least air polluted regions in the Czech Republic. Monitoring air pollution in the city of České Budějovice from 2011-2015, PM2.5 (particulate matter <2.5 µm) decreased from 20.3 ± 14.5 µg/m3 to 14.3 ± 8.6 µg/m3, but concentrations of B[a]P did not change between the years 2007-2015: 1.5 ± 0.6 ng/m3 vs. 1.4 ± 1.4 ng/m3. Higher B[a]P concentrations the winter induce genetic damage in newborns, increase frequency of micronuclei (chromosomal aberrations), deregulate genes for immunity in umbilical cord blood, and increase incidence of IUGR and LBW in newborns.
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December 2016

Impact of Air Pollution to Genome of Newborns.

Cent Eur J Public Health 2016 Dec;24 Suppl:S40-S44

University of South Bohemia, České Budějovice, Czech Republic.

The Northern Moravia Region is the most polluted region in the Czech Republic by particulate matter (PM) 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.
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http://dx.doi.org/10.21101/cejph.a4536DOI Listing
December 2016

Evaluation of 11 polycyclic aromatic hydrocarbon metabolites in urine of Czech mothers and newborns.

Sci Total Environ 2016 Oct 29. Epub 2016 Oct 29.

University of Chemistry and Technology, Prague, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28 Prague, Czech Republic. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) represent a large group of ubiquitous contaminants of the environment, including food chain where they are released as by-products of incomplete combustion of an organic matter. Epidemiological studies have shown that exposure to PAHs correlated with increased incidence of cancer. Carcinogenicity is associated mainly with metabolites that are formed during metabolic degradation of these substances in exposed organism. In this study monohydroxylated PAHs (OH-PAHs), the major metabolites excreted into urine, were determined in 531 urine samples collected from mothers and their newborns from two localities of the Czech Republic - heavily air polluted Karvina and control locality of Ceske Budejovice and in two sampling rounds - August-October 2013 (summer, less air polluted season) and January-April 2014 (winter, more air polluted season). From all targeted analytes, naphthalene-2-ol was the most abundant compound present in 100% of the samples and it represented also the analyte with the highest concentration. Median concentration of ΣOH-PAHs in the urine of children was on average 1.6 times lower compared to the respective mother which correlates with higher intake of PAHs by mothers. ΣOH-PAHs concentrations determined in mothers' urine collected in the summer were comparable in both localities. No significant increase occurred in Ceske Budejovice in winter, while in samples from the Karvina region a statistically significant difference (α=0.05) in the amount of ΣOH-PAHs was observed. The median concentrations of ΣOH-PAHs in mothers' urine samples in the winter were 1.5 times higher than in the summer in the same locality. The amounts of ΣOH-PAHs in newborns' urine from Karvina in the winter season were 1.5 times higher than in the summer collected in the same locality and 3.3 times higher when compared with the less polluted locality of Ceske Budejovice.
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http://dx.doi.org/10.1016/j.scitotenv.2016.10.165DOI Listing
October 2016

Systematic review of the use of the lymphocyte cytokinesis-block micronucleus assay to measure DNA damage induced by exposure to polycyclic aromatic hydrocarbons.

Mutat Res 2016 Oct - Dec;770(Pt A):162-169. Epub 2016 Jul 28.

Institute of Experimental Medicine AS CR, Prague, Czech Republic.

The effect of exposure to polycyclic aromatic hydrocarbons (PAHs) to induce micronuclei (MN) measured using the lymphocytes cytokinesis-block micronucleus (CBMN) assay were evaluated in 34 studies according to the exposure: 20 studies in coke oven workers, 7 studies in different occupational exposures as alluminium industry workers, rubber factory workers, road construction workers, airport workers and diesel exposed workers, 6 studies on environmentaly exposed groups as police, volunteers and children. Reviewed papers indicate that the CBMN assay is a sensitive biomarker of PAHs exposure in polluted air. Reviewed studies confirmed previous conclusions, that the frequency of MN measured using the lymphocyte CBMN is not significantly affected by smoking, females are more sensitive to PAHs than males, the frequency of MN is increased with age.
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http://dx.doi.org/10.1016/j.mrrev.2016.07.009DOI Listing
May 2017

Mapping the factors affecting the frequency and types of micronuclei in an elderly population from Southern Bohemia.

Mutat Res 2016 Nov - Dec;793-794:32-40. Epub 2016 Oct 26.

Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia.

The micronucleus assay is one of the most common methods used to assess chromosomal damage (losses or breaks) in human peripheral blood lymphocytes (PBL) in genetic toxicology. Most studies have focused on analyzing total micronuclei (MN), but identifying the content of MN can provide more detailed information. The main aim of this study was to map the factors affecting the frequency and types of micronuclei in binucleated cells (BNC) in elderly population. Fluorescence in situ hybridization using Human Pan Centromeric Chromosome Paint was used to identify centromere positive (CEN+) or centromere negative (CEN-) MN. A group of 95 men from Southern Bohemia, Czech Republic (average age 68.0±6.8 years) was followed repeatedly, in spring and fall 2014. The study participants were former workers of the uranium plant "MAPE Mydlovary" (processing uranium ore from 1962 to 1991), and controls. The general profile of individual types of MN, and the effect of the season, former uranium exposure, age, smoking status, weight, and X-ray examination on the level and type of MN were analyzed. The results of this study showed: (i) a stable profile of BNC with MN based on the number of MN during two seasons; (ii) an increase of the number of CEN+ MN from spring to fall; (iii) a lower frequency of the total MN in the exposed group than in controls with a significant difference in the percentage of aberrant cells (%AB.C.) in the fall; (iv) no clear effect of age, smoking and BMI on DNA damage in this group; (v) lower DNA damage levels in former uranium workers who received X-ray examination later in life. In summary, the results indicate a trend of seasonal changes of individual types of MN and suggest that former exposure can have a protective effect on the level of DNA damage in case of future exposure.
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http://dx.doi.org/10.1016/j.mrfmmm.2016.10.004DOI Listing
May 2017

Perinatal health in the Danube region - new birth cohort justified.

Rev Environ Health 2017 Mar;32(1-2):9-14

In 2013-2015, a consortium of European scientists - NEWDANUBE - was established to prepare a birth cohort in the Danube region, including most of the countries with the highest air pollution in Europe, the area being one-fifth of the European Union's (EU's) territory, including 14 countries (nine EU member states), over 100 million inhabitants, with numerous challenges: big socioeconomic disparities, and a region-specific environmental pollution. The consortium reflects the EU Strategy for the Danube Region Strategy (2010), which identified 11 thematic Priority Areas - one of which is the environmental risks. Birth cohorts have been established in all other areas of Europe and collaborative efforts in promoting maternal and fetal health by minimizing the environmental exposures have been initiated with national, European, and international financial support. A birth cohort in the Danube area could apply the established methodologies for prenatal exposure and birth outcome measurements and establish a platform for targeted health promotion in couples planning pregnancies. The consortium included a strong socioeconomic part focusing on the participant's active registration of exposures to environmental toxicants and health indicators of disease and wellbeing, combined with investigation of their risk-reducing behavior and interventions to change their lifestyle to avoid the adverse health risks. Willingness to pay for reducing the health risks in children is also proposed to be estimated. Further collaboration and networking is encouraged as the Danube region has several decades of experience and expertise in biomonitoring adult populations exposed environmentally or occupationally. Additionally, some countries in the Danube region launched small-scale birth cohorts encouraged by participation in several ongoing research projects.
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http://dx.doi.org/10.1515/reveh-2016-0038DOI Listing
March 2017

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

Int J Hyg Environ Health 2016 08 31;219(6):545-56. Epub 2016 May 31.

Department of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR, Prague, Czech Republic. Electronic address:

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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http://dx.doi.org/10.1016/j.ijheh.2016.05.010DOI Listing
August 2016

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine analysis by an improved ELISA: An inter-laboratory comparison study.

Free Radic Biol Med 2016 06 22;95:169-79. Epub 2016 Mar 22.

Department of Environmental and Occupational Health, Florida International University, Miami, FL, USA.

ELISA is commonly used for the detection of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of whole body oxidative stress. However, the method has been criticized for high inter-laboratory variability and poor agreement with chromatographic techniques. We performed an inter-laboratory comparison of 8-oxodG assessed in 30 urine samples and a urine spiked with four different concentrations of 8-oxodG by ELISA using standardized experimental conditions, including: sample pre-treatment with solid-phase extraction (SPE), performing analysis using a commercial kit from a single manufacturer and strict temperature control during the assay. We further compared the ELISA results with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and performed tentative identification of compounds that may contribute to the discrepancy between both methods. For all but one participating laboratory (Data 1) we observed consistent ELISA results lying mostly within 1SD of the mean 8-oxodG concentration. Mean 8-oxodG levels assessed by ELISA correlated with the data obtained by HPLC-MS/MS (R=0.679, p<0.001). The correlation improved when Data 1 were excluded from the analysis (R=0.749, p<0.001). We identified three outlying urine samples; one with an ELISA 8-oxodG concentration lower, and two with 8-oxodG levels higher, than those measured by HPLC-MS/MS. Omitting these samples further improved inter-methodology agreement (R=0.869, p<0.001). In the outliers with high 8-oxodG estimates various aromatic and heterocyclic compounds were tentatively identified using gas chromatography-mass spectrometry (GC-MS). Application of authentic standards revealed the presence of saccharides, including d-glucose and d-galactose as putative interfering substances. In summary, assay standardization improved ELISA inter-laboratory agreement, although some variability is still observed. There are still compounds contributing to overestimation of 8-oxodG by ELISA, but only in some urine samples. Thus, despite significant improvement, ELISA still should not be considered a robust alternative to chromatographic techniques.
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http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.016DOI Listing
June 2016

A novel strategy for the determination of polycyclic aromatic hydrocarbon monohydroxylated metabolites in urine using ultra-high-performance liquid chromatography with tandem mass spectrometry.

Anal Bioanal Chem 2016 Apr 9;408(10):2515-25. Epub 2016 Feb 9.

Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, University of Chemistry and Technology, Prague, Technicka 3, 166 28, Prague 6, Czech Republic.

In this study, a novel analytical approach for the determination of 11 monohydroxylated polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in urine was developed and validated. The rapid, simple and high-throughput sample preparation procedure based on ethyl acetate extraction and subsequent purification by dispersive solid-phase extraction (d-SPE) employing a Z-Sep sorbent is used for the first time. For the identification/quantification of target compounds, ultra-high-performance liquid chromatography (U-HPLC) interfaced with tandem mass spectrometry (MS/MS) was applied. The results of validation experiments performed on the Standard Reference Material (SRM) 3673 (organic contaminants in non-smokers' urine) were in accordance with the certified values. The method recoveries ranged from 77 to 114 % with the relative standard deviation lower than 20 % and the quantification limits in the range of 0.010-0.025 ng mL(-1) (except for benzo[a]pyren-3-ol with 0.9 ng mL(-1)). Within the pilot study, the new method was used for the analysis of OH-PAHs in 50 urine samples. The concentrations of ΣOH-PAHs were in the range of 0.87-63 ng mL(-1) (1600-33,000 ng g(-1) creatinine), with naphthalen-2-ol (2-OH-NAP) and phenanthren-1-ol (1-OH-PHEN) being the most abundant exposure biomarkers detected in all samples.
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http://dx.doi.org/10.1007/s00216-016-9350-1DOI Listing
April 2016

Newborns health in the Danube Region: Environment, biomonitoring, interventions and economic benefits in a large prospective birth cohort study.

Environ Int 2016 Mar 29;88:112-122. Epub 2015 Dec 29.

Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen, Denmark. Electronic address:

Background: The EU strategy for the Danube Region addresses numerous challenges including environment, health and socioeconomic disparities. Many old environmental burdens and heavily polluted areas in Europe are located in the Danube Region, consisting of 14 countries, with over 100 million people. Estimating the burden of environmental exposures on early-life health is a growing research area in Europe which has major public health implications, but the data from the Danube Region are largely missing.

Aim: This review presents an inventory of current environmental challenges, related early-life health risks, and knowledge gaps in the Danube Region, based on publicly available databases, registers, and literature, as a rationale and incentive for a new integrated project. The review also proposes the concept for the project aiming to characterize in utero exposures to multiple environmental factors and estimate their effect on early-life health, evaluate economic impact, as well as identify interventions with a potential to harness social norms to reduce emissions, exposures and health risks in the Danube Region.

Methods: Experts in environmental epidemiology, human biomonitoring and social science in collaboration with clinicians propose to establish a new large multi-center birth cohort of mother-child pairs from Danube countries, measure biomarkers of exposure and health in biological samples at birth, collect centrally measured climate, air and water pollution data, conduct pre- and postnatal surveys on lifestyle, indoor exposures, noise, occupation, socio-economic status, risk-averting behavior, and preferences; and undertake clinical examinations of children at and after birth. Birth cohort will include at least 2000 newborns per site, and a subset of at least 200 mother-child pairs per site for biomonitoring. Novel biomarkers of exposure, susceptibility, and effect will be applied, to gain better mechanistic insight. Effects of multiple environmental exposures on fetal and child growth, respiratory, allergic, immunologic, and neurodevelopmental health outcomes will be estimated. Parent's willingness to pay for reducing health risks in children will be elicited by survey, while values of cost-of-illness will be gathered from literature and national statistics. Effects of risk reducing interventions will be examined.

Conclusions: The proposed project would provide novel estimates of the burden of early childhood diseases attributable to environmental exposures and assess health impacts of different intervention scenarios in the Danube Region, in an integrated approach combining human biomonitoring, epidemiological and social science research.
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http://dx.doi.org/10.1016/j.envint.2015.12.009DOI Listing
March 2016