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2. Effect of Antioxidant Supplementation in an Elderly Population

Author

Šrám, R. J., Binková, B., Topinka, J., Kotěšovec, F., Fojtíková, I., Hanel, I., Klaschka, J., Kočišová, J., Prošek, M., Machálek, J., Claire Wilson & Associates, Chu, Ernest H. Y., editor, Bronzetti, Giorgio, editor, Hayatsu, Hikoya, editor, De Flora, Silvio, editor, Waters, Michael D., editor, and Shankel, Delbert M., editor

Published
1993
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8. Air pollution and molecular changes in age-related diseases.

Author

Hermanova, B., Riedlova, P., Dalecka, A., Jirik, V., Janout, V., and Sram, R. J.

Subjects
AIR pollution, BIOMARKERS, TELOMERES, PARTICULATE matter, DNA, SYSTEMATIC reviews, DISEASES, MOLECULAR pathology, MICRORNA, OXIDATIVE stress, MITOCHONDRIA, GENE expression, AGING
Abstract

Assessment of the impact that air contaminants have on health is difficult as this is a complex mixture of substances that varies depending on the time and place. There are many studies on the association between air pollution and increased morbidity and mortality. Before the effect of polluted air is manifested at the level of the organs, an impact can be observed at the molecular level. These include some new biomarkers, like a shortening of the mean telomere length in DNA, dysregulation of gene expression caused by microRNA levels or a variation in the copy number of mitochondrial DNA. These changes may predispose individuals to premature development of age-related diseases and consequently to shortening of life. The common attribute, shared by changes at the molecular level and the development of diseases, is the presence of oxidative stress. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Pooling birth cohorts in allergy and asthma: European union-funded initiatives-a MeDALL, CHICOS, ENRIECO, and GALEN joint paper: CHICOS study group ENRIECO study group GA2LEN study group

Author

Bousquet, Jean, Anto, Josep, Sunyer, Jordi, Nieuwenhuijsen, Mark, Vrijheid, Martine, Keil, Thomas, Akdis, M., Auffray, C., Postma, D. S., Valenta, R., Haahtela, T., Cambon-Thomsen, A., Lambrecht, B. N., Akdis, C. A., Annesi-Maesano, I., Arno, A., Bachert, C., Ballester, F., Basagana, X., Baumgartner, U., Bindslev-Jensen, C., Brunekreef, B., Chatzi, L., Eller, E., Forastiere, F., Garcia-Aymerich, J., Guerra, S., Gehring, U., Hammad, H., Heinrich, J., Hohmann, C., Kauffmann, F., Kerkhof, M., Kogevinas, M., Koppelman, G. H., Kowalski, M. L., Kull, I., Lau, S., Lodrup-Carlsen, K. C., Lupinek, C., Maier, D., Makela, M. J., Martinez, F. D., Momas, I., Nawijn, M. C., Neubauer, A., Oddie, S., Palkonen, S., Reitamo, S., Rial-Sebbag, E., Salapatas, M., Siroux, V., Smagghe, D., Smit, H. A., Torrent, M., Toskala, E., van Oosterhout, A. J. M., Varaso, R., von Hertzen, L., Wickman, M., Wijmenga, C., Zuberbier, T., Burney, P. G., Van Cauwenberge, P., Bonini, S., Fokkens, W. J., Kramer, U., Mullol, J., Nizankowska-Mogilnicka, E., Papadopoulos, N., Alm, B., Alm, J., Arshad, S. H., Bravi, F., Canonica, G. W., Custovic, A., Dubakiene, R., Fantini, M. P., Gjomarkaj, M., Halken, S., Host, A., Howarth, P., Kuehni, C., Lotvall, J., Mommers, M., Porta, D., Radon, K., Ring, J., Roberts, G., Schünemann, H. J., Simpson, A., Szczecklik, A., Thijs, C., Todo-Bom, A., Valovirta, E., van Steen, K., Von Berg, A., von Mutius, E., Wahn, U., Wennergren, G., Wijga, A. H., Zock, J. P., Duijts, L., Jaddoe, V., Lawlor, D., Lucas, P., Magnus, P., Merletti, F., Nybo Andersen, A. M., Raat, H., Stoltenberg, C., Casas, M., Bergström, A., Carmichael, A., Chen, C. -M., Cordier, S., Eggesbø, M., Fernández, M. F., Fernández-Somoano, A., Grazuleviciene, R., Karvonen, A. M., Koppen, G., Krämer, U., Kuehni, C. E., Majewska, R., Patelarou, E., Skaalum Petersen, M., Pierik, F. H., Polanska, K., Richiardi, L., Santos, A. C., Slama, R., Sram, R. J., Tischer, C., Toft, G., Trnovec, T., Vandentorren, S., Vardavas, C., Vrijkotte, T. G. M., Wilhelm, M., Bousquet, Jean, Anto, Josep, Sunyer, Jordi, Nieuwenhuijsen, Mark, Vrijheid, Martine, Keil, Thoma, Akdis, M., Auffray, C., Postma, D.S., Valenta, R., Haahtela, T., Cambon-Thomsen, A., Lambrecht, B.N., Akdis, C.A., Annesi-Maesano, I., Arno, A., Bachert, C., Ballester, F., Basagana, X., Baumgartner, U., Bindslev-Jensen, C., Brunekreef, B., Chatzi, L., Eller, E., Forastiere, F., Garcia-Aymerich, J., Guerra, S., Gehring, U., Hammad, H., Heinrich, J., Hohmann, C., Kauffmann, F., Kerkhof, M., Kogevinas, M., Koppelman, G.H., Kowalski, M.L., Kull, I., Lau, S., Lodrup-Carlsen, K.C., Lupinek, C., Maier, D., Makela, M.J., Martinez, F.D., Momas, I., Nawijn, M.C., Neubauer, A., Oddie, S., Palkonen, S., Reitamo, S., Rial-Sebbag, E., Salapatas, M., Siroux, V., Smagghe, D., Smit, H.A., Torrent, M., Toskala, E., van Oosterhout, A.J.M., Varaso, R., von Hertzen, L., Wickman, M., Wijmenga, C., Zuberbier, T., Burney, P.G., Van Cauwenberge, P., Bonini, S., Fokkens, W.J., Kramer, U., Mullol, J., Nizankowska-Mogilnicka, E., Papadopoulos, N., Alm, B., Alm, J., Arshad, S.H., Bravi, F., Canonica, G.W., Custovic, A., Dubakiene, R., Fantini, M.P., Gjomarkaj, M., Halken, S., Host, A., Howarth, P., Kuehni, C., Lotvall, J., Mommers, M., Porta, D., Radon, K., Ring, J., Roberts, G., Schünemann, H.J., Simpson, A., Szczecklik, A., Thijs, C., Todo-Bom, A., Valovirta, E., van Steen, K., Von Berg, A., von Mutius, E., Wahn, U., Wennergren, G., Wijga, A.H., Zock, J.P., Duijts, L., Jaddoe, V., Lawlor, D., Lucas, P., Magnus, P., Merletti, F., Nybo Andersen, A.M., Raat, H., Stoltenberg, C., Casas, M., Bergström, A., Carmichael, A., Chen, C.-M., Cordier, S., Eggesbø, M., Fernández, M.F., Fernández-Somoano, A., Grazuleviciene, R., Karvonen, A.M., Koppen, G., Krämer, U., Kuehni, C.E., Majewska, R., Patelarou, E., Skaalum Petersen, M., Pierik, F.H., Polanska, K., Richiardi, L., Santos, A.C., Slama, R., Sram, R.J., Tischer, C., Toft, G., Trnovec, T., Vandentorren, S., Vardavas, C., Vrijkotte, T.G.M., and Wilhelm, M.

Subjects
Allergy, Risk Factor, Immunology, CHICOS, Longitudinal Studie, Environmental Exposure, Asthma, Europe, MeDALL, ENRIECO, Hypersensitivity, Multicenter Studies as Topic, Immunology and Allergy, European Union, Cohort Studie, Birth cohort, Human
Abstract

Long-term birth cohort studies are essential to understanding the life course and childhood predictors of allergy and the complex interplay between genes and the environment (including lifestyle and socioeconomic determinants). Over 100 cohorts focusing on asthma and allergy have been initiated in the world over the past 30 years. Since 2004, several research initiatives funded under the EU Framework Program for Research and Technological Development FP6-FP7 have attempted to identify, compare, and evaluate pooling data from existing European birth cohorts (GA2LEN: Global Allergy and European Network, FP6; ENRIECO: Environmental Health Risks in European Birth Cohorts, FP7; CHICOS: Developing a Child Cohort Research Strategy for Europe, FP7; MeDALL: Mechanisms of the Development of ALLergy, FP7). However, there is a general lack of knowledge about these initiatives and their potentials. The aim of this paper is to review current and past EU-funded projects in order to make a summary of their goals and achievements and to suggest future research needs of these European birth cohort networks. © 2012 S. Karger AG, Basel.

Published
2013

15. Early growth and the risk of childhood asthma: A meta-analysis of 147,000 European children

Author

Sonnenschein-Van Voort, A. M. M., Arends, L. R., Jongste, J. C., Annesi-Maesano, I., Barros, H., Basterrechea, M., Bisgaard, H., Chatzi, L., Corpeleijn, E., Correia, S., Craig, L. C., Devereux, G., Di Oregon, V., Cristian Dogaru, Dostal, M., Duchen, K., Eggesbo, M., Ent, C. K., Fantini, M. P., Forastiere, F., Frey, U., Gehring, U., Gugten, A. C., Hanke, W., Henderson, A. J., Heude, B., Iniguez, C., Inskip, H. M., Keil, T., Kelleher, C. C., Kogevinas, M., Kreiner-Moller, E., Kuehni, C. E., Kupers, L. K., Lancz, K., Larsen, P. S., Lau, S., Ludvigsson, J., Mommers, M., Andersen, A. M. N., Palkovicova, L., Pike, K. C., Pizzi, C., Polanska, K., Porta, D., Richiardi, L., Roberts, G., Schmidt, A., Sram, R. J., Sunyer, J., Thijs, C., Torrent, M., Viljoen, K., Wijga, A. H., Vrijheid, M., Jaddoe, V. W. V., Duijts, L., A.M.M. Sonnenschein-van der Voort, L.R. Arend, J.C. de Jongste, I. Annesi-Maesano, H. Barro, M. Basterrechea, H. Bisgaard, L. Chatzi, E. Corpeleijn, S. Correia, L.C. Craig, G. Devereux, V. Di Gregori, C.M. Dogaru, M. Dostal, K. Duchen, M. Eggesbo, C.K. van der Ent, M.P. Fantini, F. Forastiere, U. Frey, U. Gehring, A.C. van der Gugten, W. Hanke, A.J. Henderson, B. Heude, C. Iñiguez, H.M. Inskip, T. Keil, C.C. Kelleher, M. Kogevina, E. Kreiner-Moller, C.E. Kuehni, L.K. Küper, K. Lancz, P.S. Larsen, S. Lau, J. Ludvigsson, M. Mommer, A.M. Nybo Andersen, L. Palkovicova, K.C. Pike, C. Pizzi, K. Polanska, D. Porta, L. Richiardi, G. Robert, A. Schmidt, R.J. Sram, J. Sunyer, C. Thij, M. Torrent, K. Viljoen, A.H. Wijga, M. Vrijheid, and V.W.V. Jaddoe and L. Duijts

Subjects
LONGITUDINAL STUDY, CHILDREN, asthma
Abstract

Background. Low birth weight, preterm birth and rapid infant growth seem to be associated with increased risks of childhood asthma. We examined the association of birth and infant growth characteristics with the risks of preschool wheezing and school age asthma using data from 147,252 subjects of 31 European cohort studies. Methods. Studies were eligible if they included children from 1989 onwards, had information on at least gestational age and weight at birth, and preschool wheezing (1-4 years) or school-age asthma (5-10 years). Adjusted pooled odds ratios (OR) from random effect models were calculated, and ORs from individual participant data were used to assess the combined effect of birth weight and gestational age. Results. Compared with term birth, preterm birth (< 37 weeks) was positively associated with increased risks of preschool wheezing and school-age asthma, independent of birth weight (OR 1.34 (1.25, 1.43) and 1.40 (1.18, 1.67)). Birth weight was not associated with preschool wheezing and school-age asthma after adjustment for gestational age at birth. Infant weight gain was positively associated with preschool wheezing and school-age asthma (OR 1.83 (1.61, 2.08) and 1.62 (1.22, 2.14) per 500 gram weight gain per month). We observed the strongest effects on preschool wheezing and school-age asthma for children born preterm with a high birth weight for gestational age, compared with term born children with an appropriate birth weight for gestational age (OR 2.40 (1.53, 3.75) and 2.77 (1.56, 4.95)). Conclusions. Preterm birth and higher infant weight gain, but not low birth weight, are associated with increased risks of wheezing and asthma in childhood.

Published
2013

16. Genomic analysis suggests higher susceptibility of children to air pollution

Author

Leeuwen, D. M., Marie Pedersen, Hendriksen, P. J. M., Boorsma, A., Herwijnen, M. H. M., Gottschalk, R. W. H., Kirsch-Volders, M., Lisbeth E. Knudsen, Sram, R. J., Bajak, E., Delft, J. H. M., Kleinjans, J. C. S., and TNO Kwaliteit van Leven

Subjects
Adult, Male, Parents, RNA Splicing, air pollution, data analysis, environmental exposure, environmental health, Physiological Sciences, cancer risk, immune response, Nuclear Family, blood analysis, gene expression profiling, genomics, micronucleus, Humans, controlled study, Genetic Predisposition to Disease, human, Child, Czech Republic, nucleosome, article, cancer susceptibility, parent, female, priority journal, Gene Expression Regulation, Health, child health, gene expression, RNA, Receptors, Chemokine, transcriptome
Abstract

Differences in biological responses to exposure to hazardous airborne substances between children and adults have been reported, suggesting children to be more susceptible. Aim of this study was to improve our understanding of differences in susceptibility in cancer risk associated with air pollution by comparing genome-wide gene expression profiles in peripheral blood of children and their parents. Gene expression analysis was performed in blood from children and parents living in two different regions in the Czech Republic with different levels of air pollution. Data were analyzed by two different approaches: one method first selected significantly differentially expressed genes and analyzed these gene lists for overrepresented biological processes, whereas the other applied the T-profiler tool to directly perform pathway analyses on the total gene set without preselection of significantly modulated gene expressions. In addition, gene expressions in both children and adults were investigated for associations with micronuclei frequencies. Both analysis approaches returned considerably more genes or gene groups and pathways that significantly differed between children from both regions than between parents. Very little overlap was observed between children and adults. The two most important biological processes or molecular functions significantly modulated in children, but not in adults, are nucleosome and immune response related. Our study suggests differences between children and adults in relation to air pollution exposure at the transcriptome level. The findings underline the necessity of implementing environmental health policy measures specifically for protecting children's health. © The Author 2008. Published by Oxford University Press. All rights reserved.

Published
2008

18. Imaging and semiquantitation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human cervix, vuvla, placenta and prostate using Immunohistochemistry (ICH) and the Automated Cellular Imaging System (ACIS).

Author

Pratt, M. M., Sirajuddin, P., Castle, P. E., Shiffman, M., Phillips, D. H., Afework, S., Ragavan, N., Martin, Francis L, Sram, R. J., Manchester, D. K., Olivero, O. A., Poirier, M. C., Pratt, M. M., Sirajuddin, P., Castle, P. E., Shiffman, M., Phillips, D. H., Afework, S., Ragavan, N., Martin, Francis L, Sram, R. J., Manchester, D. K., Olivero, O. A., and Poirier, M. C.

Abstract

Epidemiological and laboratory studies have shown significant associations between PAH exposure and subsequent development of cancer in various organs. Molecular dosimetry of DNA adduct formation typically involves tissue DNA extraction followed by DNA adduct analysis using techniques incapable of observing specific cells within a complex tissue. Here we report localization and semi-quantitation of PAH-DNA adducts in paraffin-embedded sections of human cervix, vulva, placenta and prostate utilizing IHC with an antibody generated against DNA modified with (+/-)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). Serial sections were stained with hematoxylin (to identify nuclei), specific anti-BPDE-DNA antiserum (to visualize adducts) or immunogen-absorbed anti-BPDE-DNA serum (for background). Semi-quantitation was achieved by comparison of test sample nuclear color intensity with a standard curve of human keratinocytes exposed to increasing concentrations of BPDE and analyzed for BPDE-DNA adducts by both IHC/ACIS and quantitative BPDE-DNA immunoassay. A survey of cervix from 75 individuals, placenta from 14 individuals, vulva from 19 individuals and prostate from 5 individuals has revealed large inter-individual variability in PAH-DNA adduct levels in these reproductive organ tissues. The highest concentrations of PAH-DNA adducts were observed in the basal epithelial cells of human cervix and vulva, in the cytotrophoblast cells lining the chorionic villi of the placenta and in the endothelial cells lining the ducts of the prostate. Comparison with the standard curve revealed PAH-DNA adduct concentrations ranging from ∼12 (limit of detection) to approximately 190 adducts/108 nucleotides. The study shows that many if not most individuals have PAH-DNA adducts in cervical, vulvar and prostate tissue that could reflect short- or long-term PAH exposures, while the placental PAH-DNA adducts clearly represent short-term exposures. The non-destructive DNA a

Published
2006

19. Genome-wide differential gene expression in children exposed to air pollution in the Czech Republic

Author

van Leeuwen, D M, van Herwijnen, M H M, Pedersen, Marie, Knudsen, Lisbeth E., Kirsch-Volders, M, Sram, R J, Staal, Y C M, Bajak, E, van Delft, J H M, Kleinjans, J C S, van Leeuwen, D M, van Herwijnen, M H M, Pedersen, Marie, Knudsen, Lisbeth E., Kirsch-Volders, M, Sram, R J, Staal, Y C M, Bajak, E, van Delft, J H M, and Kleinjans, J C S

Abstract

Udgivelsesdato: 2006-Aug-30, The Teplice area in the Czech Republic is a mining district where elevated levels of air pollution including airborne carcinogens, have been demonstrated, especially during winter time. This environmental exposure can impact human health; in particular children may be more vulnerable. To study the impact of air pollution in children at the transcriptional level, peripheral blood cells were subjected to whole genome response analysis, in order to identify significantly modulated biological pathways and processes as a result of exposure. Using genome-wide oligonucleotide microarrays, we investigated differential gene expression in children from the Teplice area (n=23) and compared them with children from the rural control area of Prachatice (n=24). In an additional approach, individual gene expressions were correlated with individual peripheral blood lymphocyte micronuclei frequencies, in order to evaluate the linkage of individual gene expressions with an established biomarker of effect that is representative for increased genotoxic risk. Children from the Teplice area showed a significantly higher average micronuclei frequency than Prachatice children (p=0.023). For considerable numbers of genes, the expression differed significantly between the children from the two areas. Amongst these genes, considerable numbers of genes were observed to correlate significantly with the frequencies of micronuclei. The main biological process that appeared significantly affected overall was nucleosome assembly. This suggests an effect of air pollution on the primary structural unit of the condensed DNA. In addition, several other pathways were modulated. Based on the results of this study, we suggest that transcriptomic analysis represents a promising biomarker for environmental carcinogenesis.

Published
2006

22. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Author

Bonassi, S., primary, Norppa, H., additional, Ceppi, M., additional, Stromberg, U., additional, Vermeulen, R., additional, Znaor, A., additional, Cebulska-Wasilewska, A., additional, Fabianova, E., additional, Fucic, A., additional, Gundy, S., additional, Hansteen, I.-L., additional, Knudsen, L. E., additional, Lazutka, J., additional, Rossner, P., additional, Sram, R. J., additional, and Boffetta, P., additional

Published
2008
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25. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

Author

UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Léonard, Albert, Gerber, G B, Stecca, C., Rueff, J., Borba, H, Farmer, P B, Sram, R J, Czeizel, A E, Kalina, I, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Léonard, Albert, Gerber, G B, Stecca, C., Rueff, J., Borba, H, Farmer, P B, Sram, R J, Czeizel, A E, and Kalina, I

Abstract

Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided limita

Published
1999

36. HVRII of mtDNA in cord blood cells of newborn children and in their saliva 10 years later

Author

Schmuczerova, J., Torokova, P., Kujanova, M., Cechova, H., Jan Topinka, Dostal, M., Sram, R. J., and Brdicka, R.

Subjects
Male, Polymorphism, Genetic, Air Pollution, Infant, Newborn, Humans, Female, Child, Fetal Blood, Saliva, DNA, Mitochondrial, Czech Republic, Follow-Up Studies
Abstract

Comparison of hypervariable region II nucleotide sequences of mitochondrial DNA obtained from cord blood cells and saliva cells of the same individual at birth and after ten years revealed a few differences at the so-called mutation hot spots (three transitions and three indels within the C-tract). The personal identity of samples was proved by short tandem repeat profiling. Comparison of individuals living in two regions that differ by air pollution, however, did not reveal statistically significantly increased number of mutations in the population from the region of poorer environmental conditions, although indicating such tendency.

39. Monitoring genotoxic exposure in uranium miners

Author

Vesely, D., Sram, R. J., Topinka, J., Bavorova, H., Stejskalova, J., Rossner, P., Dobias, L., Rericha, V., Binkova, B., and Vesela, D.

Subjects
THRESHOLD limit values (Industrial toxicology)
Published
1993

41. Transcriptome alterations in maternal and fetal cells induced by tobacco smoke.

Author

Votavova H, Dostalova Merkerova M, Fejglova K, Vasikova A, Krejcik Z, Pastorkova A, Tabashidze N, Topinka J, Veleminsky M Jr, Sram RJ, and Brdicka R

Subjects
Adolescent, Adult, Cohort Studies, Cotinine blood, Female, Fetal Blood metabolism, Fetus pathology, Humans, Infant, Newborn, Oligonucleotide Array Sequence Analysis, Placenta metabolism, Pregnancy, RNA chemistry, RNA genetics, Real-Time Polymerase Chain Reaction, Smoking blood, Smoking metabolism, Young Adult, Placenta pathology, Smoking adverse effects, Smoking genetics, Transcriptome physiology
Abstract

Objectives: Maternal smoking has a negative effect on all stages of pregnancy. Tobacco smoke-related defects are well established at the clinical level; however, less is known about molecular mechanisms underlying these pathologic conditions. We thus performed a comprehensive analysis of transcriptome alterations induced by smoking in maternal and fetal cells., Study Design: Samples of peripheral blood (PB), placenta (PL), and cord blood (UCB) were obtained from pregnant smokers (n = 20) and gravidas without significant exposure to tobacco smoke (n = 52). Gene expression profiles were assayed by Illumina Expression Beadchip v3 for analysis of 24,526 transcripts. The quantile method was used for normalization. Differentially expressed genes were analyzed in the Limma package and the P-values were corrected for multiple testing. Unsupervised hierarchical clustering was performed using average linkage and Euclidean distance. The enrichment of deregulated genes in biological processes was analyzed in DAVID database., Results: Comparative analyses defined significant deregulation of 193 genes in PB, 329 genes in PL, and 49 genes in UCB of smokers. The deregulated genes were mainly related to xenobiotic metabolism, oxidative stress, inflammation, immunity, hematopoiesis, and vascularization. Notably, functional annotation of the affected genes identified several deregulated pathways associated with autoimmune diseases in the newborns of smokers., Conclusions: The study demonstrated maternal smoking causes significant changes in transcriptome of placental and fetal cells that deregulate numerous biological processes important for growth and development of the fetus. An activation of fetal CYP genes showed a limited ability of the placenta to modulate toxic effects of maternal tobacco use., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Published
2011
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42. HVRII of mtDNA in cord blood cells of newborn children and in their saliva 10 years later.

Author

Schmuczerová J, Töröková P, Kujanová M, Cechová H, Topinka J, Dostál M, Sram RJ, and Brdička R

Subjects
Air Pollution, Child, Czech Republic, DNA, Mitochondrial analysis, DNA, Mitochondrial blood, Female, Follow-Up Studies, Humans, Infant, Newborn, Male, DNA, Mitochondrial genetics, Fetal Blood chemistry, Polymorphism, Genetic, Saliva chemistry
Abstract

Comparison of hypervariable region II nucleotide sequences of mitochondrial DNA obtained from cord blood cells and saliva cells of the same individual at birth and after ten years revealed a few differences at the so-called mutation hot spots (three transitions and three indels within the C-tract). The personal identity of samples was proved by short tandem repeat profiling. Comparison of individuals living in two regions that differ by air pollution, however, did not reveal statistically significantly increased number of mutations in the population from the region of poorer environmental conditions, although indicating such tendency.

Published
2011

43. The use of biomarkers for risk assessment: Reporting from the INTARESE/ENVIRISK Workshop in Prague.

Author

Smolders R, Bartonova A, Boogaard PJ, Dusinska M, Koppen G, Merlo F, Sram RJ, Vineis P, and Schoeters G

Subjects
Humans, Risk Assessment, Biomarkers analysis, Environmental Exposure analysis, Environmental Monitoring methods
Abstract

This publication is a report on the workshop "The use of biomarkers for risk assessment" which took place in November 2007 in Prague, the Czech Republic. The main aim of the workshop was to bring together a broad international audience with a particular interest in the development and application of human biomonitoring (HBM) and biomarkers for environmental health research, and to provide a state-of-the art overview of the potential values and pitfalls of biomarkers in risk assessment. Throughout the presentations and the subsequent discussions, it was shown that human biomonitoring is a highly plastic and versatile tool for the unraveling of the link between contaminants in the environment and potentially associated health effects in the general population. Although it offers a means to integrate exposure through different environmental compartments, to integrate exposure over time, to include individual risk factors and genetic susceptibility, exposure biomarkers would greatly benefit from standardized, accurate and sensitive detection methods and toxicokinetic data. Effect biomarkers on the other hand need to be put into their relevant public health perspective, and well validated, mechanistically sound dose-response relationships are essential. New developments, such as in vitro assays and "-omics", may drastically improve our knowledge on the causal mechanisms behind environmental health associations and will allow for a more informed linkage of toxicological and epidemiological reality., (Copyright 2010 Elsevier GmbH. All rights reserved.)

Published
2010
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44. Frequency of chromosomal aberrations in Prague mothers and their newborns.

Author

Rossnerova A, Balascak I, Rossner P Jr, and Sram RJ

Subjects
Adult, Chromosome Painting, Czech Republic, Female, Fetal Blood, Humans, In Situ Hybridization, Fluorescence, Maternal Age, Pregnancy, Translocation, Genetic, Air Pollutants toxicity, Chromosome Aberrations, Infant, Newborn, Maternal Exposure adverse effects, Mutagens toxicity, Polycyclic Aromatic Hydrocarbons toxicity
Abstract

The capital city of Prague is one of the most polluted areas of the Czech Republic. The impact of air pollution on the level of chromosomal aberrations was systematically studied: analyses were performed using fluorescence in situ hybridization (FISH) with whole-chromosome painting for chromosomes #1 and #4. In the present study, we analyzed the levels of stable (one-way and two-way translocations) and unstable (acentric fragments) chromosomal aberrations in 42 mothers living in Prague and in their newborns. The average age of the mothers was 29 years (range, 20-40 years). Blood samples were collected from October 2007 to February 2008. The average levels of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) and benzo[a]pyrene (B[a]P) in respirable particles (PM2.5), as determined by stationary monitoring, were 21.0+/-12.3 ng/m(3) and 2.9+/-1.8 ng/m(3), respectively. We did not observe any effect of either c-PAH or B[a]P exposure on the genomic frequency of translocations (per 100 cells, F(G)/100) in either group due to their similar exposure during the winter months. The mean values of F(G)/100 representing stable aberrations were 0.09+/-0.13 vs 0.80+/-0.79 (p<0.001) for newborns vs mothers, indicating a significant increase of F(G)/100 with age. On the other hand, the frequency of unstable aberrations did not differ between the two groups. Our results demonstrate how the patterns of different types of aberration differed between newborns and mothers: we observed 64.3% unstable aberrations and 35.7% stable aberrations in newborns vs 19.7% and 80.3% in mothers, respectively. Our results indicate that after birth the frequencies of aberrations are very low and that the aberrations are represented mainly by acentric fragments. The changes observed in mothers show a shift to stable aberrations represented mainly by two-way translocations. The mother's age affected the level of aberrations in newborns: the group of children born to older mothers (31-40 years) had significantly increased F(G)/100 levels., (Copyright 2010 Elsevier B.V. All rights reserved.)

Published
2010
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45. Effect of maternal tobacco smoke exposure on the placental transcriptome.

Author

Bruchova H, Vasikova A, Merkerova M, Milcova A, Topinka J, Balascak I, Pastorkova A, Sram RJ, and Brdicka R

Subjects
Adult, Cohort Studies, Female, Gene Expression Profiling methods, Humans, Infant, Newborn, Oligonucleotide Array Sequence Analysis methods, Placenta metabolism, Pregnancy, RNA, Messenger biosynthesis, RNA, Messenger genetics, Smoking metabolism, Placenta physiology, Prenatal Exposure Delayed Effects genetics, Smoking genetics
Abstract

Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious neonatal health problems and chronic lifelong disabilities for the children (e.g., mental retardation, learning problems). To study the effects of tobacco smoke on the placental transcriptome, we performed gene expression profiling on placentas from women exposed to tobacco smoke in pregnancy (N = 12) and from those without significant exposure (N = 64). Gene expression profiles were determined by Illumina HumanRef-8 v2 Expression BeadChips with 18,216 gene probes. Microarray data were normalized by quantile method and filtered for a detection P-value <0.01. Differential gene expression was determined by moderated t-statistic. A linear model was fitted for each gene given a series of arrays using lmFit function. Multiple testing correction was performed using the Benjamini and Hochberg method. Abundant levels of transcripts were found for genes encoding placental hormones (CSH1, CSHL1), pregnancy-specific proteins (PSG3, PSG4, PAPPA), and hemoglobins (HBB, HBG, HBA). Comparative analysis of smokers vs nonsmokers revealed the differential expression of 241 genes (P < 0.05). In smoker cohort, we detected high up-regulation of xenobiotic genes (CYP1A1, CYP1B1, CYB5A, COX412), collagen genes (e.g., COL6A3, COL1A1, COL1A2), coagulation genes (F5, F13A1) as well as thrombosis-related genes (CD36, ADAMTS9, GAS6). In smokers, we identified deregulated genes that show tissue non-specific induction and may be considered as general biomarkers of tobacco smoke exposure. Further, we also found genes specifically deregulated in the exposed placentas. Functional annotation analysis suggested processes and pathways affected by tobacco smoke exposure that may represent molecular mechanisms of smoke-induced placental abnormalities., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Published
2010
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46. Genetic polymorphisms influence the susceptibility of men to sperm DNA damage associated with exposure to air pollution.

Author

Rubes J, Rybar R, Prinosilova P, Veznik Z, Chvatalova I, Solansky I, and Sram RJ

Subjects
Adult, Chromatin genetics, Cotinine urine, Cytochrome P-450 CYP1A1 genetics, Cytochrome P-450 CYP1A1 metabolism, DNA Repair Enzymes metabolism, Folic Acid metabolism, Genotype, Glutathione Transferase genetics, Glutathione Transferase metabolism, Humans, Male, Police, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Smoking, Xeroderma Pigmentosum Group D Protein genetics, Xeroderma Pigmentosum Group D Protein metabolism, Air Pollutants, Occupational adverse effects, DNA Damage genetics, DNA Fragmentation drug effects, DNA Repair Enzymes genetics, Polymorphism, Genetic, Spermatozoa drug effects
Abstract

The purpose of the present study was to investigate the impact of carcinogenic polycyclic aromatic hydrocarbons and volatile organic compounds on sperm quality in a group of city policemen in Prague during a period of increased concentrations of ambient air-pollutants (winter season) compared to a period of low exposure (spring). Polymorphisms in metabolic genes (CYP1A1, EPHX1, GSTM1, GSTP1, GSTT1), folic acid metabolism genes (MTR, MTHFR) and DNA repair genes (XRCC1, XPD6, XPD23, hOGG1) were evaluated in these men as potential modifiers of associations between air pollution exposure and changes in sperm quality. The study population was a group of 47 policemen working in the center of the city. Seasonal differences in exposure were verified by ambient and personal monitoring. Markers of sperm injury included semen volume, sperm concentration, sperm morphology, sperm motility, and sperm DNA damage measured with the sperm chromatin structure assay The sperm chromatin structure assay (SCSA) includes a measure of DNA damage called DNA Fragmentation Index (DFI). The % of cells with detectable DFI (detDFI) by this assay includes sperm with either medium or high DNA damage; the term hDFI is used to define the % of sperm with only high DNA damage. The assay also detects immature sperm defined by high density staining (HDS). No significant differences were found in any of the standard semen parameters between the sampling periods except for vitality of sperms. Both DFI and HDS were significantly higher in winter than in spring samples for all men and for non-smokers. At the bivariate level, significant associations between hDFI or detDFI and polymorphisms of the repair genes XRCC1, XPD6 and XPD23 were observed. In multivariate models, polymorphisms of the genes XPD6, XPD23 and CYP1A1MspI were associated with hDFI and HDS. Moreover, HDS was significantly associated with polymorphisms in GSTM1 gene.

Published
2010
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47. Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part II. Oxidative damage.

Author

Rossner P Jr, Milcova A, Libalova H, Novakova Z, Topinka J, Balascak I, and Sram RJ

Subjects
8-Hydroxy-2'-Deoxyguanosine, Adult, Blood Proteins analysis, Cotinine analysis, DNA Adducts blood, Deoxyguanosine analogs & derivatives, Deoxyguanosine metabolism, Enzyme-Linked Immunosorbent Assay, F2-Isoprostanes metabolism, Female, Fetal Blood chemistry, Humans, Infant, Newborn, Lipid Peroxidation, Lymphocytes drug effects, Maternal-Fetal Exchange, Oxidation-Reduction, Placenta metabolism, Polycyclic Aromatic Hydrocarbons blood, Pregnancy, Protein Carbonylation, Vitamin A analysis, Vitamin E analysis, Young Adult, Air Pollutants blood, Biomarkers blood, Maternal Exposure, Oxidative Stress, Smoking
Abstract

Oxidative damage to macromolecules may have numerous negative health consequences. We measured oxidative damage to DNA, proteins and lipids in 80 newborns and 79 mothers, analyzed the effect of mother's tobacco smoke exposure on oxidative stress, and assessed correlations between oxidative stress markers and bulky and PAH (polycyclic aromatic hydrocarbons)-specific DNA adducts. Mean levels (+/-S.D.) of 8-oxodeoxyguanosine (8-oxodG) per 10(5) dG in the placenta were 2.85+/-0.78; we did not see a difference between 8-oxodG levels in newborns born to mothers exposed and unexposed to tobacco smoke. Protein carbonyl levels, a marker of protein oxidation, were comparable in the umbilical cord and in maternal venous blood plasma (17.4+/-3.2 and 17.6+/-4.2nmol/ml plasma in newborns and mothers, respectively, p=0.66). Lipid peroxidation measured as levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) in plasma was significantly higher in newborns than in mothers (362+/-129 and 252+/-130pg/ml in newborns and mothers, respectively, p<0.001). We did not find any effect of tobacco smoke exposure on either biomarker in any group. Levels of both protein carbonyls and 15-F(2t)-IsoP in cord blood significantly correlated with those in maternal plasma (p<0.001). 8-oxodG levels positively correlated with plasma carbonyls in cord plasma, as well as with cotinine levels (marker of tobacco smoke exposure) in maternal plasma. 8-oxodG levels also correlated with bulky DNA adducts in lymphocyte DNA of newborns and mothers and with PAH-DNA adducts in the placenta. Our results showed higher lipid peroxidation in newborns than in mothers, close correlation of analyzed oxidative stress markers between newborns and mothers, and a relationship between oxidative stress and induction of DNA adducts.

Published
2009
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48. Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part I: bulky DNA adducts.

Author

Topinka J, Milcova A, Libalova H, Novakova Z, Rossner P Jr, Balascak I, and Sram RJ

Subjects
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide metabolism, Adult, Cotinine blood, DNA Adducts metabolism, Enzyme-Linked Immunosorbent Assay, Female, Fetal Blood metabolism, Humans, Infant, Newborn, Lymphocytes drug effects, Maternal-Fetal Exchange, Pregnancy, Young Adult, Air Pollutants blood, Biomarkers blood, DNA Adducts blood, Fetus blood supply, Maternal Exposure, Placenta drug effects, Polycyclic Aromatic Hydrocarbons blood, Smoking
Abstract

(32)P-postlabelling and PAH-ELISA using the antiserum #29 were employed to analyze DNA adducts in venous and umbilical cord blood and the placenta of 79 mothers giving birth to 80 living babies in Prague (Czech Republic). Ambient air exposure was measured by stationary measurements of basic air pollutants (PM2.5, c-PAHs) during the entire pregnancy. Tobacco smoke exposure was assessed by questionnaire data and by plasma cotinine levels. The total DNA adduct levels in the lymphocytes of mothers and newborns were elevated by 30-40% (p<0.001) compared with the placenta. B[a]P-like DNA adduct (adduct with the identical chromatographic mobility on TLC as major BPDE derived DNA adduct) levels were elevated in the blood of mothers compared with the placenta and the blood of newborns (p<0.05 and p<0.01). In tobacco smoke-exposed mothers, higher DNA adduct levels in the blood of mothers and newborns compared with the placenta were found (p<0.001), whereas the total and B[a]P-like adduct levels were comparable in the blood of mothers and newborns. B[a]P-like adducts were elevated in the blood of mothers unexposed to tobacco smoke compared with that of corresponding newborns and the placenta (p<0.01). Total and B[a]P-like DNA adducts were increased in the placenta of tobacco smoke-exposed compared with unexposed mothers (p<0.001 and p<0.01). In lymphocytes of tobacco smoke-exposed mothers, the comparison of total adduct levels (1.18+/-0.67 vs. 0.92+/-0.28) and B[a]P-like DNA adducts (0.22+/-0.12 adducts/10(8) nucleotides vs. 0.15+/-0.06 adducts/10(8) nucleotides) with newborns indicated a 30-40% increase of adducts in mothers. Almost equal PAH-DNA adduct levels were detected by anti-BPDE-DNA ELISA in the placenta of tobacco smoke-exposed and -unexposed mothers. Our results suggest a protective effect of the placental barrier against the genotoxic effect of some tobacco smoke components between the circulation of mother and child. We found a correlation between adduct levels in the blood of mothers and newborns.

Published
2009
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49. The impact of air pollution on the levels of micronuclei measured by automated image analysis.

Author

Rossnerova A, Spatova M, Rossner P, Solansky I, and Sram RJ

Subjects
Adult, Automation, Case-Control Studies, Cotinine urine, Humans, Male, Micronucleus Tests, Police, Smoking adverse effects, Air Pollution adverse effects, Carcinogens, Environmental pharmacology, Image Processing, Computer-Assisted, Lymphocytes drug effects, Micronuclei, Chromosome-Defective chemically induced, Polycyclic Aromatic Hydrocarbons pharmacology
Abstract

The measurement of micronuclei (MN) in human peripheral blood lymphocytes is frequently used in molecular epidemiology as one of the preferred methods for assessing chromosomal damage resulting from environmental mutagen exposure. In the present study, we evaluated the effect of exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), volatile organic compounds (VOC) and smoking on the frequency of MN in a group of 56 city policemen living and working in Prague. The average age of the participants was 34+/-6 years. The study was conducted on the same subjects in February and May 2007. The concentrations of air pollutants were obtained from personal and stationary monitoring. A statistically significant decrease in the levels of pollutants was observed in May when compared with February, with the exception of toluene levels measured by stationary monitoring. The frequency of MN was determined by the automatic image scoring (MetaSystems Metafer 4, version 3.2.1) of DAPI-stained slides. The results of the image analysis indicated a significant difference in the frequency of MN (mean levels 7.32+/-3.42 and 4.67+/-2.92, for February and May, respectively). Our study suggests that automatic image analysis of MN is a highly sensitive method for evaluating the effect of c-PAHs and confirms that there are no differences between smokers and nonsmokers. These results demonstrate the ability of c-PAHs to increase MN frequency, even if the exposure to c-PAHs occurred up to 60 days before the collection of biological material. Our work is the first human biomonitoring study focused on the measurement of MN by automated image analysis for assessing chromosomal damage as a result of environmental mutagen exposure.

Published
2009
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50. Genetic variability of HVRII mtDNA in cord blood and respiratory morbidity in children.

Author

Schmuczerova J, Brdicka R, Dostal M, Sram RJ, and Topinka J

Subjects
Adult, Child, Child, Preschool, Female, Humans, Infant, Inhalation Exposure, Male, Pregnancy, Smoking adverse effects, Air Pollutants toxicity, Complementarity Determining Regions, DNA, Mitochondrial, Fetal Blood, Maternal Exposure, Polymorphism, Genetic, Respiration Disorders genetics
Abstract

Genetic polymorphisms were examined using direct sequencing of the hypervariable region II (HVRII) in the D-loop of mtDNA in the cord blood of 355 children living in two areas of the Czech Republic - the industrial district of Teplice and the agricultural district of Prachatice. The incidence of the most frequent nucleotide variants of HVRII, C150T (10.1%), T152C (19.7%), T195C (19.7%) and 309.nC (41.4% for 309.2C and 13.8% for 309.3C), and the respiratory morbidity at the ages of 0-2 years and 2-6 years were investigated, considering many other factors such as locality, gender, ethnicity, heating by coal in household, maternal age, asthma bronchiale, allergic rhinitis, pollinosis, conjunctivitis and maternal tobacco exposure during and after pregnancy. We found that the T195C transversion in HVRII is connected with an increased risk of early childhood (0-2 years) bronchitis (RR 1.38, p=0.034, 95% CI 1.04-1.85) and with increased risk of otitis media in children aged 2-6 years (RR 1.62, p=0.032, 95% CI 1.04-2.53). Another polymorphism, 309.nC, is associated with an increased risk of bronchitis in children aged 2-6 years (RR 1.46, p=0.030, 95% CI 1.04-2.06). The results indicate that genetic polymorphisms in mtDNA may be an important factor not only for various types of cancers and neurodegenerative diseases, but also for respiratory morbidity in children.

Published
2009
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