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Micronuclei and their connection with intracellular innate immunity and viral infection
Knoblochová, Kateřina ; Bruštíková, Kateřina (advisor) ; Španielová, Hana (referee)
Micronuclei are tiny structures that contain nuclear DNA and a membrane derived from the nucleus. They emerge in cells that have been exposed to severe stress factors, such as viral infections, radiation, or genotoxic substances. While micronuclei have long been used as markers of genotoxic stress, the mechanism of their formation and internal processes are not yet fully understood. DNA enclosed inside micronuclei is restructured in an atypical manner, which may induce mutations and accelerate oncogenic transformation of the cell. Due to these processes micronuclei can also act as reservoirs of immunostimulatory nucleic acids, which may potentially be detected by molecular sensors. Therefore, studying micronuclei is significant in relation to the activation of signaling pathways that are part of the innate intracellular immunity. This work summarizes the current knowledge about micronuclei and their connection to innate intracellular immunity and viral infection. Keywords: micronuclei, innate immunity, molecular sensors, chromotripsis
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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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Cytogenetic methods in genotoxicology
Bártů, Linda ; Daňková, Pavlína (advisor) ; Langová, Martina (referee)
We are constantly exposed to a variety of factors which may be a cause of DNA mutations. The influence of mutagens of physical, chemical and biological origin is studied by genotoxicology. Ionic radiation is among the most common physical mutagens, benzene, vinylchloride or some drugs represent the chemical mutagens, while some viruses and may act as biological mutagens. The repair mechanisms of double strand breaks can be divided into those that require HRR-homologous sequences and those that may use of microhomologies consisting of a short DNA sequence (NHEJ). Both mechanisms can lead to aberrations of chromosomes, if they are not precise. Acquired chromosomal aberrations include translocation, common in cancer cells; deletion; or the production of acentric fragments, dicentrics and rings. Chromatid aberrations includes chromatid breaks and chromatide exchanges. There are various methods for detecting/examining such mutations and these can be categorised according to the phases of the cell cycle. The basic method is clasic Giemsa stain which reveals the most of aberrations except translocations and inversions and numeric abnormalities in metaphasic cells. Another way of testing mutagenicity is determining the rate of sister chromatide exchange; or the so called micronucleus test used to measure...
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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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Cytogenetic methods in genotoxicology
Bártů, Linda ; Langová, Martina (referee) ; Daňková, Pavlína (advisor)
We are constantly exposed to a variety of factors which may be a cause of DNA mutations. The influence of mutagens of physical, chemical and biological origin is studied by genotoxicology. Ionic radiation is among the most common physical mutagens, benzene, vinylchloride or some drugs represent the chemical mutagens, while some viruses and may act as biological mutagens. The repair mechanisms of double strand breaks can be divided into those that require HRR-homologous sequences and those that may use of microhomologies consisting of a short DNA sequence (NHEJ). Both mechanisms can lead to aberrations of chromosomes, if they are not precise. Acquired chromosomal aberrations include translocation, common in cancer cells; deletion; or the production of acentric fragments, dicentrics and rings. Chromatid aberrations includes chromatid breaks and chromatide exchanges. There are various methods for detecting/examining such mutations and these can be categorised according to the phases of the cell cycle. The basic method is clasic Giemsa stain which reveals the most of aberrations except translocations and inversions and numeric abnormalities in metaphasic cells. Another way of testing mutagenicity is determining the rate of sister chromatide exchange; or the so called micronucleus test used to measure...
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