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Role of chromosomal aberrations to evaluate genetic risk of exposure to carcinogens.
Rössnerová, Andrea ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Kuglík, Petr (referee)
(in English) Air pollution is a serious worldwide problem associated with the risk of cancer. The negative effect of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), including benzo[a]pyrene (B[a]P), on human health is analyzed using specific biomarkers. Among them biomarkers of early effect play an important role. This work summarizes the results of cytogenetic analyses performed by fluorescence in situ hybridization (FISH) (whole chromosome painting of chromosomes #1 and #4) and automated image analysis of micronuclei (MN). During the analyses a total set of 1304 samples was analyzed by the FISH method and 885 samples by the automated image analysis of MN. Studied groups including city policemen, garage men, bus drivers, administrative workers, mothers, newborns, healthy children and children with bronchial asthma and laboratory workers were from Prague, Ostrava and Ceske Budejovice. The locations significantly differed in levels of air pollutants and the type of air pollution. The exposure of participants of the study was assessed by personal and stationary monitoring. The impact of other factors including age, smoking or intake of vitamins was also evaluated in these studies. The results obtained by the FISH method in Prague showed the impact of seasonal variability of concentrations of...
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Modulation of sporadic colorectal cancer risk by polymorphisms and haplotypes of mismatch repair genes
Tulupova, Elena ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Slabý, Ondřej (referee)
Sporadic colorectal cancer (CRC) is a common disease with complex aetiology and diverse molecular phenotypes. Failure of DNA repair systems is one of the leading determinants of cancer onset and development. The efficiency of these systems and susceptibility to cancer can be affected by genotype variations, including common single nucleotide polymorphisms (SNPs). In this work, an association between SNPs and haplotypes of DNA mismatch repair (MMR) genes, SNPs and their combinations in other DNA repair genes, and a risk of sporadic CRC was investigated in a hospital-based case-control study. As result of our study, certain MMR SNPs and haplotypes altered CRC risk, as demonstrated for the first time in the Czech population. Individual SNPs in DNA repair genes seem to have a limited effect on CRC risk, with possible modification by age or smoking. Several of the associations observed were site-specific, confirming the molecular heterogeneity of CRC. DNA repair capacity varies significantly between individuals, between different tissues of the same organism, and also between malignant and normal cells. To assess the background level of this variability, the association between SNPs in DNA repair genes and the individual DNA repair capacity in healthy individuals was investigated. Several polymorphisms...
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Genotoxicity of organic air pollutants studied by DNA adduct detection
Sevastyanova, Oksana ; Šrám, Radim (advisor) ; Stiborová, Marie (referee) ; Velemínský, Petr (referee)
heterozygotů.Lze Ííci,žeasociacehladin DNA aduktůs oběma genotypybyl pozorovánzvláštěpři vysokéexpozici k-PAU (l. odběr), coŽ je ve shodě s našimi předcházejícímivýsledky (Topinkaetal..1997t. Zár.ěrc.nrlz.. konstalt)\ll1. Žc. tato studie prokazuje,že D\A adu\lr r ]r::].:.':eci: oStrb erponor'anýchzvýšeným h!gJ!:..:: !.-!,!. ..j z::cčištěnénlor.zdušíjsou vhodným i.: :..:.-l..::::.-: . ;:cxr aktirnídál.ky'př.ínronaznačujícím,zda '..' r. .] '\.]. zlcc tětt-ttolátkámje neboneníspojenase zvýšeným -. ..:-:*:,:.':]iIrra karcinogennímrizikem. zÁvĚny In vitro studie . Nebuněčný systém Ve spojení s citlivou metodou 3,P- postlabelingu je vhodným modelovým systémem pro stanovenígenotoxickéhopotenciálu EoM, zejménaextraktů obsahujícíchk-PAU, a také pro rozlišování přímých a nepřímých genotoxikantů v komplexních směsích environmentálníchpolutantů. . Buňky HepG2 jsou vhodné in vitro modelovébuňky pro testování genotoxického potenciálu komplexních směsí, protožejsou schopny metabolicky aktivovat k-PAU jako nejvýznamnější genotoxické sloŽky EoM a vykazují monotonní dávkovou závislost v širokéškále koncentrací EOM. . Buňky HEL jsou dostatečnecitlivé pro stanoveníDNA aduktůjednotlivýchPAU. ale docházíu nich k silnéinhibici tvorbyaduktův podmínkáchmodelovýchsměsíPAU a také jsouméněcitlivév reálnj'chEo\Í. o...
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Modulation of sporadic colorectal cancer risk by polymorphisms and haplotypes of mismatch repair genes
Tulupova, Elena ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Slabý, Ondřej (referee)
Sporadic colorectal cancer (CRC) is a common disease with complex aetiology and diverse molecular phenotypes. Failure of DNA repair systems is one of the leading determinants of cancer onset and development. The efficiency of these systems and susceptibility to cancer can be affected by genotype variations, including common single nucleotide polymorphisms (SNPs). In this work, an association between SNPs and haplotypes of DNA mismatch repair (MMR) genes, SNPs and their combinations in other DNA repair genes, and a risk of sporadic CRC was investigated in a hospital-based case-control study. As result of our study, certain MMR SNPs and haplotypes altered CRC risk, as demonstrated for the first time in the Czech population. Individual SNPs in DNA repair genes seem to have a limited effect on CRC risk, with possible modification by age or smoking. Several of the associations observed were site-specific, confirming the molecular heterogeneity of CRC. DNA repair capacity varies significantly between individuals, between different tissues of the same organism, and also between malignant and normal cells. To assess the background level of this variability, the association between SNPs in DNA repair genes and the individual DNA repair capacity in healthy individuals was investigated. Several polymorphisms...
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Epidemiology analysis of the effect of air pollution on health at regional scale
Rychlíková, Eva ; Šrám, Radim (advisor) ; Bartoňová, Alena (referee) ; Holcátová, Ivana (referee)
Epidemiology analysis of the effect of air pollution on health at regional scale MUDr. Eva Rychlíková ABSTRACT Work involves a health impact assessment of the air pollution of aerosol particles at the some important steps. It describes evidence on air pollution exposure in vulnerable groups of population and searches for the effects. An exposure is a component of causal chains of diseases coming from external origin. And just because it is the main condition. If there is no exposure, there is no health risk. For a possibility to prevent disease we need to know an exposure. We investigated exposure with an activity questionaire in the three groups of population whose would be to the environmental factors, mainly air pollution, vulnerable. The personal exposure was monitored in a group of children. In preparing the questionnaire, we respect the recommendation of US EPA and WHO. Sensitivity is determined by the properties of the organism, specific period of its evolution, lifestyle and behaviour, the circumstances under which exposure to pollution occurs. We evaluated the effects on health which included short-time mortality, long-time mortality and respiratory morbidity in children.The air pollution and its development were evaluated in the Ustecky Region, Region of Prague and Moravskoslezsky region. The...
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Role of chromosomal aberrations to evaluate genetic risk of exposure to carcinogens.
Rössnerová, Andrea ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Kuglík, Petr (referee)
(in English) Air pollution is a serious worldwide problem associated with the risk of cancer. The negative effect of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), including benzo[a]pyrene (B[a]P), on human health is analyzed using specific biomarkers. Among them biomarkers of early effect play an important role. This work summarizes the results of cytogenetic analyses performed by fluorescence in situ hybridization (FISH) (whole chromosome painting of chromosomes #1 and #4) and automated image analysis of micronuclei (MN). During the analyses a total set of 1304 samples was analyzed by the FISH method and 885 samples by the automated image analysis of MN. Studied groups including city policemen, garage men, bus drivers, administrative workers, mothers, newborns, healthy children and children with bronchial asthma and laboratory workers were from Prague, Ostrava and Ceske Budejovice. The locations significantly differed in levels of air pollutants and the type of air pollution. The exposure of participants of the study was assessed by personal and stationary monitoring. The impact of other factors including age, smoking or intake of vitamins was also evaluated in these studies. The results obtained by the FISH method in Prague showed the impact of seasonal variability of concentrations of...
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The impact of polluted air on oxidative damage to DNA.
Švecová, Vlasta ; Šrám, Radim (advisor) ; Stiborová, Marie (referee) ; Rössner, Pavel (referee)
IMPACTS OF AIR POLLUTION ON OXIDATIVE DNA DAMAGE Vlasta Svecova Department of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, v.v.i. Videnska 1083, 142 20 Prague 4 Tel.: +420 241 062 669, fax.: +420 241 062 785, e-mail: svecova@biomed.cas.cz This thesis deal with impacts of air pollution on human health. The biomarkers of biologically effective dose, biomarkers of oxidative damage to DNA, lipids and proteins, were studied. We aimed at importance of individual pollutants, measured the personal exposure to these pollutants and analyzed the biomarkers of oxidative damage to macromolecules. c-PAHs (carcinogenic polycyclic aromatic hydrocarbons) bound to airborne PM2.5 (particulate matter ≤ 2.5 µm) and volatile organic compounds (benzene, toluene, ethylbenzene and m,p,o-xylenes, BTEX) were studied as ones of the biologically most important pollutants. Personal and outdoor concentrations of c-PAHs together with personal exposure to BTEX were measured. The concentrations of pollutants were correlated with biomarker levels in different seasons and localities. Bus drivers in Prague, 6-10 years old children from Teplice and Prachatice and policemen with office workers from Ostrava region were the model populations. Oxidative damage to DNA were measured by 8-oxodeoxyguanosine (8-oxodG), 15-F2t-...
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Vliv komplexních směsí látek ve znečištěném ovzduší na zdravotní stav rizikových populačních skupin
Výzkumný ústav veterinárního lékařství, Brno ; Český hydrometeorologický ústav, Praha ; Ústav experimentální medicíny AV ČR, Praha ; Rubeš, Jiří ; Dejmek, Jan ; Šrám, Radim ; Binková, Blanka ; Novák, Jiří
Cílem je stanovení rizika expozice nízkým hladinám komplexních směsí látek přítomných ve znečištěném ovzduší, hodnocení dlouhodobých účinků znečištění na reprodukční funkce žen i mužů v Praze a v Teplicích, hodnocení expozice biologicky aktivním látkám u vybrané populace ve vztahu ke znakům vnímavosti a životního stylu jedince, vytypování vhodných biomarkerů zátěže lidské populace polutantům v ovzduší, odhadnutí podílu dopravy na této zátěži a vypracování systému interpretace získaných dat. Svazek obsahuje zprávy o řešení jednotlivých projektů v rámci úkolu: Projekt 1: Monitorování ovzduší . Projekt 2: Genotoxicita ovzduší. Projekt 3: Expozice modelové populace. Projekt 4: Výsledky těhotenství. Projekt 5: Kvalita lidských spermií. Projekt 6: Hodnocení zdravotního rizika.
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Vliv komplexních směsí látek ve znečištěném ovzduší na zdravotní stav rizikových populačních skupin
Výzkumný ústav veterinárního lékařství, Brno ; Český hydrometeorologický ústav, Praha ; Ústav experimentální medicíny AV ČR, Praha ; Šmerhovský, Zdeněk ; Rubeš, Jiří ; Šrám, Radim ; Binková, Blanka ; Novák, Jiří
Cílem je stanovení rizika expozice nízkým hladinám komplexních směsí látek přítomných ve znečištěném ovzduší, hodnocení dlouhodobých účinků znečištění na reprodukční funkce žen i mužů v Praze a v Teplicích, hodnocení expozice biologicky aktivním látkám u vybrané populace ve vztahu ke znakům vnímavosti a životního stylu jedince, vytypování vhodných biomarkerů zátěže lidské populace polutantům v ovzduší, odhadnutí podílu dopravy na této zátěži a vypracování systému interpretace získaných dat. Svazek obsahuje zprávy o řešení jednotlivých projektů v rámci úkolu: Projekt 1: Monitorování ovzduší. Projekt 2: Genotoxicita ovzduší. Projekt 3: Expozice modelové populace. Projekt 4: Výsledky těhotenství. Projekt 5: Kvalita lidských spermií. Projekt 6: Hodnocení zdravotního rizika.
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