Effects of airborne particles on the expression status of markers of cellular toxic stress and on the release of eicosanoids, linked with inflammation and oxidative damage, remain poorly characterized. Therefore, we proposed a set of various methodological approaches in order to address complexity of PM0.5-induced toxicity. For this purpose, we used a well-characterized model of A549 pulmonary epithelial cells exposed to a non-cytotoxic concentration of ambient aerosol particle fraction PM0.5 for 24 h. Electron microscopy confirmed accumulation of PM0.5 within A549 cells, yet, autophagy was not induced. Expression profiles of various cellular stress response genes that have been previously shown to be involved in early stress responses, namely unfolded protein response, DNA damage response, and in aryl hydrocarbon receptor (AhR) and p53 signaling, were analyzed. This analysis revealed induction of GREM1, EGR1, CYP1A1, CDK1A, PUMA, NOXA and GDF15 and suppression of SOX9 in response to PM0.5 exposure. Analysis of eicosanoids showed no oxidative damage and only a weak anti-inflammatory response. In conclusion, this study helps to identify novel gene markers, GREM1, EGR1, GDF15 and SOX9, that may represent a valuable tool for routine testing of PM0.5-induced in vitro toxicity in lung epithelial cells.

• Klíčová slova
• AhR, PM0.5, early stress response, eicosanoids, inflammation, p53, ultrafine particulate matter, unfolded protein response (UPR),
• MeSH
• aerosoly MeSH
• buňky A549 MeSH
• epitelové buňky metabolismus   patologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• pevné částice toxicita   MeSH
• plíce metabolismus   patologie   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aerosoly MeSH
• látky znečišťující vzduch MeSH
• pevné částice MeSH

OBJECTIVES: This study aimed to assess the biological impact of occupational exposure to diesel exhaust (DE) including DE particles (DEP) from heavy-duty diesel-powered equipment in Norwegian tunnel finishing workers (TFW). METHODS: TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). RESULTS: PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. Levels of DNA adducts were also related to smoking habits. Seventeen miRNAs were significantly deregulated in TFW. Several of these miRNAs are related to carcinogenesis, apoptosis and antioxidant effects. Analysis of putative miRNA-gene targets revealed deregulation of pathways associated with cancer, alterations in lipid molecules, steroid biosynthesis and cell cycle. Plasma profiles showed higher levels of free AA and 15-hydroxyeicosatetraenoic acid, and lower levels of prostaglandin D2 and 9-hydroxyoctadecadienoic acid in TFW compared with referents. CONCLUSION: Occupational exposure to DE/DEP is associated with biological alterations in TFW potentially affecting lung homoeostasis, carcinogenesis, inflammation status and the cardiovascular system. Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC.

• Klíčová slova
• biomonitoring, diesel fumes, particulates, polyaromatic hydrocarbons (pahs), toxicology,
• MeSH
• adukty DNA krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• inhalační expozice analýza   MeSH
• látky znečišťující vzduch v pracovním prostředí analýza   MeSH
• leukocyty mononukleární chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• lipidy krev   MeSH
• mikro RNA krev   MeSH
• pracovní expozice škodlivé účinky   MeSH
• průřezové studie MeSH
• stavebnictví * MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Norsko MeSH
• Názvy látek
• adukty DNA MeSH
• biologické markery MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• lipidy MeSH
• mikro RNA MeSH
• výfukové emise vozidel MeSH