Hjem Publikasjoner In vitro transformation of human bronchia[...]

In vitro transformation of human bronchial epithelial cells by diesel exhaust particles. Gene expression profiling and early toxic responses

Vit. artikkel


  • 2018

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...

Rynning, Iselin; Neca, Jiri; Vrbova, Kristyna; Libalova, Helena; Rossner, Pavel; Holme, Jørn Andreas; Gutzkow, Kristine Bjerve; Afanou, Komlavi Anani; Arnoldussen, Yke Jildouw; Hruba, Eva; Skare, Øivind; Haugen, Aage; Topinka, Jan; Machala, Miroslav; Mollerup, Steen Kristen
Toxicological Sciences 166(1): 51–64
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