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Importance of DNA-adduct formation and gene expression profiling of disease candidate genes in rats exposed to bitumen fumes
The equivocal experimental and epidemiologicat evidence of bitumen fumes and the possible mechanisms of toxicity remain uncertain. This study therefore aimed at investigating the genotoxicity of bitumen fumes, the biotransformation and urinary excretion of PAHs (polycyclic aromatic hydrocarbons), and altered expression of a selected number of genes in lung, nasal epithelium, and white blood cells of rats. Notably, no dose-related signs of intolerance were observed throughout the inhalation period but dose dependent uptake of bitumen fumes was observed based on urinary excretion of PAHs and metabolites. Pyrene, a minor component in bitumen fumes, produced hydroxypyrene levels close to the detection limit in rat urine. We additionally determined DNA adduct formation by the 32.P-postlabelling assay and observed a dose and time dependent increase of 3 to 4 stable DNA adducts in lung, nasal, and alveolar epithelium. DNA adduct levels were highest in nasal epithelium. It is important to note that erythrocyte cell count in bone marrow smears was reduced in four out of six animals after 12 months of exposure, clearly demonstrating that components of bitumen fume had reached the bone marrow. Finally, we investigated by reverse transcription polymerase chain reaction regulation of genes with known functions in inflammation, asthma and other pulmonary diseases. Gene expression changed during the time of exposure. With the monooxygenases CYPlAl and CYP2G1 we observed dose dependent regulation in nasal and lung tissue. We found bitumen fumes to be genotoxic in target tissue of exposure and observed altered regulation of genes involved in the metabolic activation of polycyclic aromatic hydrocarbons and cellular inflammatory processes. These findings are consistent with the histopathology observed in the respiratory tract of rats chronically exposed to bitumen fume.
Importance of DNA-adduct formation and gene expression profiling of disease candidate genes in rats exposed to bitumen fumes
The equivocal experimental and epidemiologicat evidence of bitumen fumes and the possible mechanisms of toxicity remain uncertain. This study therefore aimed at investigating the genotoxicity of bitumen fumes, the biotransformation and urinary excretion of PAHs (polycyclic aromatic hydrocarbons), and altered expression of a selected number of genes in lung, nasal epithelium, and white blood cells of rats. Notably, no dose-related signs of intolerance were observed throughout the inhalation period but dose dependent uptake of bitumen fumes was observed based on urinary excretion of PAHs and metabolites. Pyrene, a minor component in bitumen fumes, produced hydroxypyrene levels close to the detection limit in rat urine. We additionally determined DNA adduct formation by the 32.P-postlabelling assay and observed a dose and time dependent increase of 3 to 4 stable DNA adducts in lung, nasal, and alveolar epithelium. DNA adduct levels were highest in nasal epithelium. It is important to note that erythrocyte cell count in bone marrow smears was reduced in four out of six animals after 12 months of exposure, clearly demonstrating that components of bitumen fume had reached the bone marrow. Finally, we investigated by reverse transcription polymerase chain reaction regulation of genes with known functions in inflammation, asthma and other pulmonary diseases. Gene expression changed during the time of exposure. With the monooxygenases CYPlAl and CYP2G1 we observed dose dependent regulation in nasal and lung tissue. We found bitumen fumes to be genotoxic in target tissue of exposure and observed altered regulation of genes involved in the metabolic activation of polycyclic aromatic hydrocarbons and cellular inflammatory processes. These findings are consistent with the histopathology observed in the respiratory tract of rats chronically exposed to bitumen fume.
Importance of DNA-adduct formation and gene expression profiling of disease candidate genes in rats exposed to bitumen fumes
Die Bedeutung der DNS-Adduktbildung und die Gene von Krankheitskandidaten profilierende Genexpression in Bitumendämpfen ausgesetzten Ratten
Halter, Roman (author) / Hansen, Tanja (author) / Seidel, Albrecht (author) / Ziemann, Christina (author) / Borlak, Jürgen (author)
2007
21 Seiten, 3 Bilder, 7 Tabellen, 73 Quellen
Conference paper
English
Bitumen , Dampf , Schadstoffexposition , Tierversuch , Genexpression , Krankheit , Desoxyribonukleinsäure , Reaktionsprodukt , Gen , Toxizität , Metabolit , polycyclischer aromatischer Kohlenwasserstoff , Lunge , Nase , Leukozyten , Knochenmark , Transkription (Biologie) , Polymerase-Kettenreaktion , Sekret
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