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Study of metabolism air pollutants and mutagens 3-nitrobenzanthrone and 2-nitrobenzanthrone
Čechová, Tereza ; Stiborová, Marie (advisor) ; Martínek, Václav (referee)
Nitroaromatic compounds are mutagenic and carcinogenic substances present in environment. Most of nitroaromatic compounds are potent mutagens in bacterial and mammalian systems. They are also carcinogens causing development of tumors, primarily in the liver, lung and mammary glands. 3-Nitrobenzanthrone (3-NBA, 3-nitro-7H-benz [de] anthracene-7-one) is one of the polycyclic aromatic nitro compounds possesing high toxic effects. 3-NBA is an environmental pollutant present in diesel exhaust and was also detected in soil and in rain water. 2-Nitrobenzanthrone (2-NBA, 2-nitro-7H-benz [de] anthracene-7-one) is an isomer 3-NBA, which also occurs as a pollutant in air. Although the 2-NBA is a weakly toxic substance, its high abundance in air could exhibit a high health risk to humans. This thesis investigates the metabolism of 3-NBA and its isomeric derivate, isomer 2 NBA, under anaerobic and aerobic conditions. To study the metabolism of these compounds, microsomal systems isolated from the liver of rats pretreated with Sudanem I, -naphthoflavone, phenobarbital, ethanol and pregnenolon 16-carbonitrile (PCN), the inducers of cytochromes P450 1A, 2B, 2E1 and 3A, were used. We also used mouse models, a control mouse line (wild type WT) and mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting...
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Connection between the solubility and the mutagenicity of nitrobenzanthrones in water and organic solvents
Řeboun, Martin ; Martínek, Václav (advisor) ; Hudeček, Jiří (referee)
2-Nitrobenzanthron (2-NBA) and 3-nitrobenzanthron (3-NBA) are pollutants widely occurring in the environment. The main sources of benzanthrones are combustion products (i.e. diesel exhausts, wood and cigarette smoke ...). 3-NBA is proven mutagen and carcinogen for bacteria and mammals and it is probably mutagenic also to humans. Nitronbezanthrones can form covalent adducts with purine bases in DNA after their metabolic activation. Genotoxic properties of 2-NBA are lover by 3-4 orders of magnitudes in comparison to 2-NBA, large difference in the solubility, and therefore also the difference in their bioavailability, of these isomers can be among the factors explaining this phenomenon. One of our goals was to determine the solubility of 3-NBA and 2-NBA in water and in methanol. The second objective was to determine the extinction coefficients for their solutions in water and methanol. Two different methods were employed to determine the solubility of 3-NBA and 2-NBA. The first method was based on stepwise adding of the stock solution of 3-/2-NBA in dimethylsulfoxide to excessive volume of water and simultaneous spectrophotometric verification of the Lambert-Beer law. Additional experiments confirmed the solubility of 3-/2- NBA utilizing spectrophotometric determination of 3-/2-NBA concentration in...
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Mechanism of cancerogenic effect of nitroaromates pollutants in present environment
Čechová, Tereza ; Stiborová, Marie (advisor) ; Svobodová, Martina (referee)
Nitroaromatic compounds are mutagenic and carcinogenic substances present in all environmental compartments. Polycyclic aromatic hydrocarbons react with nitrogen oxides to form nitroaromatics under the conditions that might be expected in polluted air and in combustion processes (fossil fuel combustion, waste heat recovery, metal processing, etc.). Most of nitroaromatic compounds are potent mutagens in bacterial and mammalian systems. They are also carcinogens causing cancer, primarily in the liver, lungs and mammary glands. Nitrobenzanthrones (NBA) are nitroaromatic compounds which were recently found in environmental compartments, especially in the air. 3-Nitrobenzanthrone (3-NBA, 3-nitro-7H-benz [de] anthracene-7-one) is one of the polycyclic aromatic nitro compounds with high toxic effects. 3-NBA is present in environmental pollution, in diesel exhaust and was also detected in soil and in rain water. Bachelor's thesis describes the metabolism of this substance and it also studies its mutagenic and carcinogenic effects. This work also compares the mutagenic and carcinogenic effects of 3-NBA and its derivative, isomer 2-nitrobenzanthrone (2-NBA, 2-nitro-7H-benz [de] anthracene-7-one), which also occurs as a pollutant in air. (In Czech)
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Solubility of lipophilic model carcinogens in water environment and effect of biomolecules
Řeboun, Martin ; Martínek, Václav (advisor) ; Hudeček, Jiří (referee)
2-Nitrobenzanthron (2-NBA) and 3-nitrobenzanthron (3-NBA) are pollutants widely occurring in the environment. The main sources of benzanthrones are combustion products (i.e. diesel exhausts, wood and cigarette smoke ...). 3-NBA is proven strong mutagen and carcinogen for bacteria and mammals and it is probably mutagenic also to humans, while 2- NBA shows genotoxic properties lower by 3-4 orders of magnitude. Here we consider the possibility that large difference in the solubility, and consequently also the difference in bioavailability of these isomers could be the factor partially explaining this phenomenon. One goal was to determine solubility of 2-NBA in water and compare it with 3-NBA and also with other carcinogens studied in our laboratory (Sudan I, ellipticin). Another objective was to evaluate the effect of model proteins (bovine serum albumin, lysozyme) on solubility of Sudan I and ellipticine. The last aim was to determine extinction coefficients of these compounds in water and in methanol. Two different methods were employed to determine the solubility of the model compounds. The first method was based on spectrophotometric verification of the Lambert- Beer law. The results were than compared with other method measuring concentration of a compound in saturated solution (In Czech) Key...
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Solubility of lipophilic model carcinogens in water environment and effect of biomolecules
Řeboun, Martin ; Martínek, Václav (advisor) ; Hudeček, Jiří (referee)
2-Nitrobenzanthron (2-NBA) and 3-nitrobenzanthron (3-NBA) are pollutants widely occurring in the environment. The main sources of benzanthrones are combustion products (i.e. diesel exhausts, wood and cigarette smoke ...). 3-NBA is proven strong mutagen and carcinogen for bacteria and mammals and it is probably mutagenic also to humans, while 2- NBA shows genotoxic properties lower by 3-4 orders of magnitude. Here we consider the possibility that large difference in the solubility, and consequently also the difference in bioavailability of these isomers could be the factor partially explaining this phenomenon. One of our goals was to determine the solubility of 2-NBA in water and compare it with 3-NBA and also with other carcinogens studied in our laboratory (Sudan I, ellipticin). The second aim was to determine extinction coefficients of these compounds in water and in methanol. Two different methods were employed to determine the solubility of the model compounds. The first method was based on spectrophotometric verification of the Lambert- Beer law. The results were than compared with other method utilizing determination of concentration of a compound in equilibrium with solid phase. (In Czech) Key words: solubility, UV-VIS spectroscopy, 3-nitrobenzanthrone, 2-nitrobenzanthrone, ellipticine, Sudan I
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Solubility of lipophilic model carcinogens in water environment and effect of biomolecules
Řeboun, Martin ; Martínek, Václav (advisor) ; Hudeček, Jiří (referee)
2-Nitrobenzanthron (2-NBA) and 3-nitrobenzanthron (3-NBA) are pollutants widely occurring in the environment. The main sources of benzanthrones are combustion products (i.e. diesel exhausts, wood and cigarette smoke ...). 3-NBA is proven strong mutagen and carcinogen for bacteria and mammals and it is probably mutagenic also to humans, while 2- NBA shows genotoxic properties lower by 3-4 orders of magnitude. Here we consider the possibility that large difference in the solubility, and consequently also the difference in bioavailability of these isomers could be the factor partially explaining this phenomenon. One goal was to determine solubility of 2-NBA in water and compare it with 3-NBA and also with other carcinogens studied in our laboratory (Sudan I, ellipticin). Another objective was to evaluate the effect of model proteins (bovine serum albumin, lysozyme) on solubility of Sudan I and ellipticine. The last aim was to determine extinction coefficients of these compounds in water and in methanol. Two different methods were employed to determine the solubility of the model compounds. The first method was based on spectrophotometric verification of the Lambert- Beer law. The results were than compared with other method measuring concentration of a compound in saturated solution (In Czech) Key...
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Study of metabolism air pollutants and mutagens 3-nitrobenzanthrone and 2-nitrobenzanthrone
Čechová, Tereza ; Stiborová, Marie (advisor) ; Martínek, Václav (referee)
Nitroaromatic compounds are mutagenic and carcinogenic substances present in environment. Most of nitroaromatic compounds are potent mutagens in bacterial and mammalian systems. They are also carcinogens causing development of tumors, primarily in the liver, lung and mammary glands. 3-Nitrobenzanthrone (3-NBA, 3-nitro-7H-benz [de] anthracene-7-one) is one of the polycyclic aromatic nitro compounds possesing high toxic effects. 3-NBA is an environmental pollutant present in diesel exhaust and was also detected in soil and in rain water. 2-Nitrobenzanthrone (2-NBA, 2-nitro-7H-benz [de] anthracene-7-one) is an isomer 3-NBA, which also occurs as a pollutant in air. Although the 2-NBA is a weakly toxic substance, its high abundance in air could exhibit a high health risk to humans. This thesis investigates the metabolism of 3-NBA and its isomeric derivate, isomer 2 NBA, under anaerobic and aerobic conditions. To study the metabolism of these compounds, microsomal systems isolated from the liver of rats pretreated with Sudanem I, -naphthoflavone, phenobarbital, ethanol and pregnenolon 16-carbonitrile (PCN), the inducers of cytochromes P450 1A, 2B, 2E1 and 3A, were used. We also used mouse models, a control mouse line (wild type WT) and mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting...
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Connection between the solubility and the mutagenicity of nitrobenzanthrones in water and organic solvents
Řeboun, Martin ; Martínek, Václav (advisor) ; Hudeček, Jiří (referee)
2-Nitrobenzanthron (2-NBA) and 3-nitrobenzanthron (3-NBA) are pollutants widely occurring in the environment. The main sources of benzanthrones are combustion products (i.e. diesel exhausts, wood and cigarette smoke ...). 3-NBA is proven mutagen and carcinogen for bacteria and mammals and it is probably mutagenic also to humans. Nitronbezanthrones can form covalent adducts with purine bases in DNA after their metabolic activation. Genotoxic properties of 2-NBA are lover by 3-4 orders of magnitudes in comparison to 2-NBA, large difference in the solubility, and therefore also the difference in their bioavailability, of these isomers can be among the factors explaining this phenomenon. One of our goals was to determine the solubility of 3-NBA and 2-NBA in water and in methanol. The second objective was to determine the extinction coefficients for their solutions in water and methanol. Two different methods were employed to determine the solubility of 3-NBA and 2-NBA. The first method was based on stepwise adding of the stock solution of 3-/2-NBA in dimethylsulfoxide to excessive volume of water and simultaneous spectrophotometric verification of the Lambert-Beer law. Additional experiments confirmed the solubility of 3-/2- NBA utilizing spectrophotometric determination of 3-/2-NBA concentration in...
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Mechanism of cancerogenic effect of nitroaromates pollutants in present environment
Čechová, Tereza ; Svobodová, Martina (referee) ; Stiborová, Marie (advisor)
Nitroaromatic compounds are mutagenic and carcinogenic substances present in all environmental compartments. Polycyclic aromatic hydrocarbons react with nitrogen oxides to form nitroaromatics under the conditions that might be expected in polluted air and in combustion processes (fossil fuel combustion, waste heat recovery, metal processing, etc.). Most of nitroaromatic compounds are potent mutagens in bacterial and mammalian systems. They are also carcinogens causing cancer, primarily in the liver, lungs and mammary glands. Nitrobenzanthrones (NBA) are nitroaromatic compounds which were recently found in environmental compartments, especially in the air. 3-Nitrobenzanthrone (3-NBA, 3-nitro-7H-benz [de] anthracene-7-one) is one of the polycyclic aromatic nitro compounds with high toxic effects. 3-NBA is present in environmental pollution, in diesel exhaust and was also detected in soil and in rain water. Bachelor's thesis describes the metabolism of this substance and it also studies its mutagenic and carcinogenic effects. This work also compares the mutagenic and carcinogenic effects of 3-NBA and its derivative, isomer 2-nitrobenzanthrone (2-NBA, 2-nitro-7H-benz [de] anthracene-7-one), which also occurs as a pollutant in air. (In Czech)
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