INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.

• Klíčová slova
• Alzheimer's disease (AD), air pollution, air–liquid interface (ALI), heat shock protein (HSP), next‐generation sequencing (NGS), nuclear factor erythroid 2–related factor 2 (NRF2), traffic emissions, traffic‐related air pollution (TRAP) olfactory mucosa (OM),
• MeSH
• Alzheimerova nemoc * genetika   metabolismus   MeSH
• čichová sliznice metabolismus   MeSH
• epigenomika MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• mikro RNA metabolismus   genetika   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• výfukové emise vozidel * toxicita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• látky znečišťující vzduch MeSH
• mikro RNA MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• výfukové emise vozidel * MeSH

Inhalation exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with various adverse health effects, including chronic lung diseases and cancer. Using human bronchial epithelial cell line HBE1, we investigated the effects of structurally different PAHs on tissue homeostatic processes, namely gap junctional intercellular communication (GJIC) and MAPKs activity. Rapid (<1 h) and sustained (up to 24 h) inhibition of GJIC was induced by low/middle molecular weight (MW) PAHs, particularly by those with a bay- or bay-like region (1- and 9-methylanthracene, fluoranthene), but also by fluorene and pyrene. In contrast, linear low MW (anthracene, 2-methylanthracene) or higher MW (chrysene) PAHs did not affect GJIC. Fluoranthene, 1- and 9-methylanthracene induced strong and sustained activation of MAPK ERK1/2, whereas MAPK p38 was activated rather nonspecifically by all tested PAHs. Low/middle MW PAHs can disrupt tissue homeostasis in human airway epithelium via structure-dependent nongenotoxic mechanisms, which can contribute to their human health hazards.

• Klíčová slova
• Gap junctional intercellular communication, Human bronchial epithelial cell line, Methylated anthracenes, Mitogen-activated protein kinases, Nongenotoxic mechanisms, Polycyclic aromatic hydrocarbons,
• MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   fyziologie   MeSH
• lidé MeSH
• mezerový spoj účinky léků   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy MeSH
• polycyklické aromatické uhlovodíky MeSH

The biological effects induced by complete engine emissions in a 3D model of the human airway (MucilAirTM) and in human bronchial epithelial cells (BEAS-2B) grown at the air-liquid interface were compared. The cells were exposed for one or five days to emissions generated by a Euro 5 direct injection spark ignition engine. The general condition of the cells was assessed by the measurement of transepithelial electrical resistance and mucin production. The cytotoxic effects were evaluated by adenylate kinase (AK) and lactate dehydrogenase (LDH) activity. Phosphorylation of histone H2AX was used to detect double-stranded DNA breaks. The expression of the selected 370 relevant genes was analyzed using next-generation sequencing. The exposure had minimal effects on integrity and AK leakage in both cell models. LDH activity and mucin production in BEAS-2B cells significantly increased after longer exposures; DNA breaks were also detected. The exposure affected CYP1A1 and HSPA5 expression in MucilAirTM. There were no effects of this kind observed in BEAS-2B cells; in this system gene expression was rather affected by the time of treatment. The type of cell model was the most important factor modulating gene expression. In summary, the biological effects of complete emissions exposure were weak. In the specific conditions used in this study, the effects observed in BEAS-2B cells were induced by the exposure protocol rather than by emissions and thus this cell line seems to be less suitable for analyses of longer treatment than the 3D model.

• Klíčová slova
• 3D models, cell monocultures, complete engine emissions, gene expression,
• MeSH
• biologické markery MeSH
• biologické modely * MeSH
• chaperon endoplazmatického retikula BiP MeSH
• elektrická impedance MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• exprese genu MeSH
• lidé MeSH
• muciny biosyntéza   MeSH
• respirační sliznice účinky léků   metabolismus   MeSH
• výfukové emise vozidel toxicita   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zlomy DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• HSPA5 protein, human MeSH Prohlížeč
• muciny MeSH
• výfukové emise vozidel 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

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.

• MeSH
• bronchy účinky léků   metabolismus   ultrastruktura   MeSH
• buněčné kultury MeSH
• epitelo-mezenchymální tranzice účinky léků   genetika   MeSH
• epitelové buňky účinky léků   metabolismus   ultrastruktura   MeSH
• interleukin-1beta genetika   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• pevné částice toxicita   MeSH
• poškození DNA MeSH
• stanovení celkové genové exprese MeSH
• transformované buněčné linie MeSH
• transkriptom účinky léků   MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-1beta MeSH
• látky znečišťující vzduch MeSH
• pevné částice MeSH
• výfukové emise vozidel MeSH