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The effect of air pollution on oxidative stress markers in newborns
Ambrož, Antonín ; Rössner, Pavel (advisor) ; Rubeš, Jiří (referee) ; Gábelová, Alena (referee)
In everyday life, humans are exposed to toxic substances of anthropogenic origin. These substances can also be found in the ambient air and their impact poses a long-term risk for human health. Respirable particulate matter (PM) of aerodynamic diameter < 2.5 µm (PM2.5) is intensively studied, along with carcinogenic polycyclic aromatic hydrocarbons (PAHs), bound to it, such as benzo[a]pyrene (B[a]P), a reference carcinogenic PAH. Owing to small size, PM2.5 can penetrate the human body primarily via the airways and represent an increased health risk compared to larger particles. The negative health impacts of anthropogenic PM2.5, generated e.g. by fossil fuel combustion, are linked with its small size, relatively large surface, as well as with PAHs and other substances adsorbed on PM surface. PAHs, generated by an incomplete combustion of organic matter, can enter organism either via ingestion of contaminated food, water or via inhalation of polluted air. PAHs affect organisms via genotoxic, mutagenic, carcinogenic, embryotoxic and other adverse effects. One of the common denominators of these effects is oxidative stress, which is also considered to be the main mechanism of action caused by PM in the human organism. Oxidative damage induced by reactive oxygen species (ROS) may affect any cellular...
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The effect of maternal nutrition on the newborn genome methylation
Pavlíková, Jitka ; Rössner, Pavel (advisor) ; Černá, Marie (referee) ; Hlaváč, Viktor (referee)
The maternal diet during pregnancy is an important factor involved in the epigenetic programming of the offspring. In addition to the nutritional aspect, the epigenome is also influenced by possible contaminating substances that may occur in the diet of pregnant women. An important group of these potential contaminants are persistent organic pollutants, which are compounds of mostly anthropogenic origin that persist in the environment for a long time, become part of food chains, and some of them accumulate in living organisms. These substances are being monitored for their adverse effects on organisms, and the use of some of them has already been banned or at least significantly restricted. The aim of this work was to find out whether the quality of the diet of pregnant women in the Czech Republic differs in terms of nutrition and contamination with persistent organic pollutants so much that these differences can be reflected in the methylome of newborns. The diet quality of 49 pregnant women from the Karviná and České Budějovice regions was analyzed. During the last month of pregnancy, these women recorded in detail all the food they ate for one week and at the same time collected a quarter of this food in boxes (one box for one day). Information on the quantity and quality of the diet was...
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Molecular Prognostic and Predictive Markers in Colorectal Cancer
Navvabi, Nazila ; Pitule, Pavel (advisor) ; Rössner, Pavel (referee) ; Grubhoffer, Libor (referee)
in English Colorectal cancer is currently one of the three major causes of cancer-related death. In order to help clinicians to treat colorectal cancer, it is necessary to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. This thesis aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, feces or blood) along with their restrictions. In relation to my research, the thesis will also focus on alternative splicing that has emerged as an important regulator and potential treatment target in CRC. Alterations in gene expression leading to colorectal carcinogenesis results in dysregulated levels of nucleic acids and proteins, which can be utilized for the identification of modern, minimally invasive molecular biomarkers. One of the alternative splicing factors are MBNL proteins. The goal of my work that will be presented here was to analyze gene expression of the MBNL family of regulators of alternative splicing in various stages of colorectal cancer development, together with the MBNL-target splicing events in FOXP1 and EPB41L3 genes and tumor-related CD44 variants. The study was done using...
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The role of dispersion medium on nanoparticle aggregation and size in biological systems
Červená, Tereza ; Rössnerová, Andrea ; Závodná, Táňa ; Vrbová, Kristýna ; Sikorová, Jitka ; Topinka, Jan ; Rössner ml., Pavel
The use of nanomaterials (NMs) in different areas has been rising for more than a decade. Along with this growth, there is visible development of different testing tools and approaches for measuring the actual size of nanomaterials in biological systems. Test conditions during in vitro toxicological assays are different from the standard conditions under which nanomaterials are characterized and careful evaluation of results is needed. The unique properties and range variety of NMs require the close look how the NMs behave in different dispersion medium over time. In this study we present the results of five types of well-characterized NMs (TiO2: NM-101 and NM-103, SiO2: NM-200, Ag: NM-300K and NM-302) of specific size and shape. The hydrodynamic size and Zeta potentials in suspensions were measured using a dynamic light scattering technique (DLS) (Zetasizer Nano ZS, Malvern, UK). The DLS method is suitable for spherical particles, nevertheless, all samples were measured in order to obtain a rough insight into agglomerate formation in the medium. NM300, NM302, and NM200 aggregated rapidly in the media, thus the cells would be most likely exposed to settled big aggregates then small clusters or individual particles. More stable NMs (NM100 and NM103) showed slight grow along with cultivation time or concentration corresponding to cluster formation. Cells exposed to those NMs would be in contact with small clusters and aggregates of NMs. Measured zeta potentials fluctuated around the stability limit corresponding to observed aggregation.
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Ultrafine particles and their possible role in etiology and development of neurodegenerative diseases
Topinka, Jan ; Závodná, Táňa ; Rössnerová, Andrea ; Rössner ml., Pavel
Air pollutants have been shown to cause a vast amount of different adverse health effects. These effects include impairment of many respiratory (e.g. asthma, chronic obstructive pulmonary disease) and cardiovascular (ischemic heart disease, infarction, stroke) diseases. However, in recent years, the evidence showing effects beyond the lungs and circulatory system are becoming more evident. Neurological diseases, namely Alzheimer's disease (AD) has shown to be associated with living near traffic. However, reason for this has remained unresolved until today. Our new H2020 project TUBE aims on revealing the mechanisms of action of ultrafine particles involved in neurological diseases. The TUBE consortium includes experts in areas of aerosol technology, emission research, engine and fuel research, human clinical studies, epidemiology, emission inventories, inhalation toxicology, neurotoxicology and disease mechanism studies. This enables research of resolving the effects of nanoparticles from different traffic modes for both air quality and concomitant toxic effect of these air pollutants. We will investigate adverse effects of air pollutants using cell cultures, animal exposures and volunteered human exposures as well as the material from epidemiological cohort study. These are going to be compared according to inflammatory, cytotoxic and genotoxic changes and furthermore beyond the current state of the art to neurotoxic and brain health effects. With this approach, we are aiming to a comprehensive understanding of the adverse brain effects of nanoparticles from traffic.
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Toxic responses in human lung epithelial cells (BEAS-2B) exposed to particulate matter exhaust emissions from gasoline and biogasoline
Závodná, Táňa ; Líbalová, Helena ; Vrbová, Kristýna ; Sikorová, Jitka ; Vojtíšek-Lom, M. ; Beránek, V. ; Pechout, M. ; Kléma, J. ; Cigánek, M. ; Machala, M. ; Neča, J. ; Rössner ml., Pavel ; Topinka, Jan
Motor vehicle emissions substantially contribute to air pollution worldwide and cause serious health problems. While the deleterious effects of diesel exhaust particulate matter (PM) have been widely studied, much less attention is paid to toxicity of PM emitted by gasoline engines although they also produce considerable amount of PM. The primary objective of this research was to assess toxic potencies of exhaust PM released by conventional gasoline engine fueled with neat gasoline (EU) or gasoline-ethanol blend (15% ethanol, v/v, E15). Despite a similar particle mass (mu g PM/kg fuel) produced by both fuels, PM emitted by E15 contained higher amount of harmful polycyclic aromatic hydrocarbons (PAH) as suggested by chemical analysis. To examine the toxicity of organic PM constituents, human lung BEAS-2B cells were exposed for 4h and 24h to a subtoxic dose of E0 and E15 PM organic extracts. We used genome scale transcriptomic analysis to characterize the toxic response and to identify modulated biological process and pathways. Whereas 4h exposure to both PM extracts resulted in modulation of similar genes and pathways related to lipid and steroid metabolism, activation of PPAR alpha, oxidative stress and immune response, 24h exposure was more specific for each extract, although both induced expression of PAH-metabolic enzymes, modulated metabolism of lipids or activated PPAR alpha, E15 additionally deregulated variety of other pathways. Overall, the PM mass produced by both fuels was similar, however, higher PAH content in E15 PM organic extract may have contributed to more extensive toxic response particularly after 24h exposure in BEAS-2B cells.
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Males-females differences in the spectrum of chromosomal aberrations in the group of nanocomposites production workers
Rössnerová, Andrea ; Pelcová, D. ; Ždímal, Vladimír ; Elzeinova, Fatima ; Margaryan, Hasmik ; Chvojková, Irena ; Topinka, Jan ; Schwarz, Jaroslav ; Ondráček, Jakub ; Koštejn, Martin ; Komarc, M. ; Vlčková, Š. ; Fenclová, Z. ; Lischková, L. ; Dvořáčková, Š. ; Rössner ml., Pavel
An increase in the use of nanomaterials (NM) has been witnessed in many areas of human life. Therefore, assessment of genotoxicity of NM and nanoparticles (NP) is one of the main objectives of genetic toxicology. Despite this fact, human cytogenetic studies following the exposure to NP are still rare. Moreover, no relevant information on possible differences in sensitivity to NP related to gender is available.\n\nIn this study we periodically (in September 2016, 2017 and 2018; pre-shift and post-shift each year) analyzed a group of workers (both genders), working long time in nanocomposites research, and matched controls. Aerosol exposure monitoring of particulate matter including nano-sized fractions was carried out during working shift. Micronucleus assay using Human Pan Centromeric probes, was applied to distinguish, besides the frequency of total MN in binucleated cells (BNC), also other types of chromosomal damage (losses and breaks). Moreover, whole-chromosome painting (WCP) for autosome #1 and both gonosomes (X and Y) were applied in third sampling period (2018) with the aim to identify the particular structural and numerical chromosomal aberrations.\n\nObtained results showed: (i) differences in the risk of exposure to NP related to individual working processes (welding, smelting and machining); (ii) differences in chemical composition of nano-fraction; (iii) no effect of chronic exposure of NP (total MN) opposite to significant effect of acute exposure; (iv) gender-related DNA damage differences (females seem to be more sensitive to chromosomal losses). Additional data from WCP suggested increased frequency of numerical aberrations in gonosomes.
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Biomarkers of Oxidative Stress and Inflammation in Researches Exposed to Nanoparticles by Inhalation During the Handling of Nanocomposites.
Pelclová, D. ; Ždímal, Vladimír ; Schwarz, Jaroslav ; Komarc, M. ; Vlčková, Š. ; Fenclová, Z. ; Lischková, L. ; Dvořáčková, Š. ; Rössnerová, Andrea ; Rössner ml., Pavel
At present, little is known about the health effects in the workers processing nanocomposites. In our study, 20 researchers (41.8 +/- 11.4 y/o), handling nanocomposites for 17.8 +/- 10.0 years were examined pre-shift and post-shift, together with 21 controls (42.7 +/- 11.5 y/o). Biomarkers of oxidative stress derived from lipids, nucleic acids, proteins and markers of inflammation were analyzed in the exhaled breath condensate (EBC). Aerosol exposure was monitored during three nanoparticle generation operations: smelting, welding and nanocomposite machining. Mass concentrations during these operations ranged from 0.120 to 1.840 mg/m(3), and median particle number concentrations from 4.8x10(4) to 5.4x10(5) particles/cm(3). Nanoparticles accounted for 40 to 95 % of particles, with Fe and Mn prevailing. Significant elevations were already seen in most oxidative stress markers and in several inflammation markers in the pre-shift samples relative to the controls. Significant associations were found between working in nanocomposite synthesis and the majority of EBC biomarkers. Chronic bronchitis was more frequent in researchers. A minor, but significant post-shift decrease of lung function parameters was found. We conclude that workers in nanocomposite synthesis may be at risk of developing airway disorders with time. From all the markers analyzed in EBC, the following markers were most robust and could be recommended for preventive examinations: 8-hydroxy-2-deoxyguanosine (8-OHdG) and 5-hydroxymethyl uracil (5-OHMeU) from nucleic acids, o-tyrosine (o-Tyr) and 3-nitrotyrosine (3-NOTyr) from proteins, and malondialdehyde and aldehydes C6-C13 from lipids. Among the markers of inflammation, tumor necrosis factor (TNF) and leukotriene B4 appeared to be the most useful.
Plný tet: PDF
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The effect of nanoparticles on functional and regenerative properties of mesenchymal stem cells
Dostálová, Dominika ; Rössner, Pavel (advisor) ; Grobárová, Valéria (referee)
Mesenchymal stem cells (MSCs) represent a type of stem cells, localized in various tissues, where they are involved in the regeneration process. Because of their properties, MSC are tested for cell-based therapy. However, the treatment of injuries is often associated with bacterial infections, which complicate the process of healing. To establish a sterile environment, metallic nanoparticles (NPs) with proven antibacterial properties can be applied, for improving the healing process. Mechanisms of the antibacterial effect of NPs are non-specific and may cause the damage of eukaryotic cells. The aim of this thesis was to evaluate the effect of three antibacterial metallic NPs (silver, copper oxide and titanium dioxide) on the functional and regenerative properties of MSCs. The effect of NPs on the metabolic activity, differentiational potential, expression of genes for immunoregulatory molecules and production of cytokines by MSCs was determined. Additionally, the immunoregulatory properties of MSCs after cultivation with NPs were tested. The results showed that the metabolic activity was reduced in the presence of silver and copper oxide NPs, with the decrease dependent on the type of the tested NPs. The expression of selected immunoregulatory molecules was inhibited and the immunoregulatory...
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Oxidative damage by organic extracts from urban air particulate matter
Hanzalová, Kateřina ; Rössner, Pavel (advisor) ; Machala, Miroslav (referee)
The aim of this master thesis was to investigate the ability of selected individual carcinogenic polycyclic aromatic hydrocarbons (c-PAHs: benzo[a]pyrene, B[a]P; dibenzo[a,l]pyrene, DB[a,l]P), an artificial mixture of c-PAHs (c-PAH mix) and extractable organic matter (EOM) from urban air particulate matter (PM) to induce oxidative damage in vitro. Two cell lines (human hepatoma cells, HepG2, and human diploid lung fibroblasts, HEL) were treated for 24 h and 48 h with various concentrations of compounds or mixtures. The studied oxidative stress markers included 8-oxodeoxyguanosine (8-oxodG) as a marker of oxidative DNA damage, 15-F2t-isoprostane (15-F2t-IsoP) as a marker of lipid peroxidation and protein carbonyl groups as a marker of oxidative damage to proteins. The response of the cell lines to the tested compounds and mixtures differed substantially. In summary the results demonstrate the ability of EOM to induce oxidative damage to DNA and lipids after 24 h of treatment and to proteins after 48 h, in HepG2 cells. The effect of c-PAHs was substantially less. The induction of oxidative damage by c- PAHs and EOM in HEL cells was weak. Since c-PAHs had lower ability to cause oxidative damage that was limited only to longer incubation periods, it is probable that other components of EOM are responsible for...
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