| Autor: |
Rynning I; Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, N-0304 Oslo, Norway., Neca J; Department of Chemistry and Toxicology, Veterinary Research Institute, 621 00 Brno, Czech Republic., Vrbova K; Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic., Libalova H; Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic., Rossner P Jr; Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic., Holme JA; Division of Infection Control, Environment and Health, Department of Air and Noise., Gützkow KB; Division of Infection Control, Department of Molecular Biology, Norwegian Institute of Public Health, N-0304 Oslo, Norway., Afanou AKJ; Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, N-0304 Oslo, Norway., Arnoldussen YJ; Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, N-0304 Oslo, Norway., Hruba E; Department of Chemistry and Toxicology, Veterinary Research Institute, 621 00 Brno, Czech Republic., Skare Ø; Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, N-0304 Oslo, Norway., Haugen A; Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, N-0304 Oslo, Norway., Topinka J; Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20 Prague, Czech Republic., Machala M; Department of Chemistry and Toxicology, Veterinary Research Institute, 621 00 Brno, Czech Republic., Mollerup S; Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, N-0304 Oslo, Norway. |
| Abstrakt: |
Occupational exposure to diesel exhaust may cause lung cancer in humans. Mechanisms include DNA-damage and inflammatory responses. Here, the potential of NIST SRM2975 diesel exhaust particles (DEP) to transform human bronchial epithelial cells (HBEC3) in vitro was investigated. Long-term exposure of HBEC3 to DEP led to increased colony growth in soft agar. Several DEP-transformed cell lines were established and based on the expression of epithelial-to-mesenchymal-transition (EMT) marker genes, one of them (T2-HBEC3) was further characterized. T2-HBEC3 showed a mesenchymal/fibroblast-like morphology, reduced expression of CDH1, and induction of CDH2 and VIM. T2-HBEC3 had reduced migration potential compared with HBEC3 and little invasion capacity. Gene expression profiling showed baseline differences between HBEC3 and T2-HBEC3 linked to lung carcinogenesis. Next, to assess differences in sensitivity to DEP between parental HBEC3 and T2-HBEC3, gene expression profiling was carried out after DEP short-term exposure. Results revealed changes in genes involved in metabolism of xenobiotics and lipids, as well as inflammation. HBEC3 displayed a higher steady state of IL1B gene expression and release of IL-1β compared with T2-HBEC3. HBEC3 and T2-HBEC3 showed similar susceptibility towards DEP-induced genotoxic effects. Liquid-chromatography-tandem-mass-spectrometry was used to measure secretion of eicosanoids. Generally, major prostaglandin species were released in higher concentrations from T2-HBEC3 than from HBEC3 and several analytes were altered after DEP-exposure. In conclusion, long-term exposure to DEP-transformed human bronchial epithelial cells in vitro. Differences between HBEC3 and T2-HBEC3 regarding baseline levels and DEP-induced changes of particularly CYP1A1, IL-1β, PGE2, and PGF2α may have implications for acute inflammation and carcinogenesis. |
