The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched controls. The study group consisted of 73.2% males and 26.8% females. Aerosol exposure monitoring during a working shift (involving welding, smelting, machining) to assess the differences in exposure to particulate matter (PM) including nanosized fractions <25-100 nm, and their chemical analysis, was carried out. A micronucleus assay using Human Pan Centromeric probes, was applied to distinguish between the frequency of centromere positive (CEN+) and centromere negative (CEN-) micronuclei (MN) in the binucleated cells. This approach allowed recognition of the types of chromosomal damage: losses and breaks. The monitoring data revealed differences in the exposure to NP related to individual working processes, and in the chemical composition of nanofraction. The cytogenetic results of this pilot study demonstrated a lack of effect of long-term (years) exposure to NP (total frequency of MN, P = 0.743), although this exposure may be responsible for DNA damage pattern changes (12% increase of chromosomal breaks-clastogenic effect). Moreover, short-term (daily shift) exposure could be a reason for the increase of chromosomal breaks in a subgroup of researchers involved in welding and smelting processes (clastogenic effect, P = 0.037). The gender and/or gender ratio of the study participants was also an important factor for the interpretation of the results. As this type of human study is unique, further research is needed to understand the effects of long-term and short-term exposure to NP.

• MeSH
• cytogenetické vyšetření * metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrojaderné testy metody   MeSH
• mladý dospělý MeSH
• mutageny škodlivé účinky   MeSH
• nanočástice * MeSH
• pevné částice * škodlivé účinky   MeSH
• pilotní projekty MeSH
• pracovní expozice * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mutageny MeSH
• pevné částice * MeSH

The inhalation or application of nanoparticles (NPs) has serious impacts on immunological reactivity. However, the effects of NPs on the immune system are influenced by numerous factors, which cause a high variability in the results. Here, mice were exposed to a three month continuous inhalation of copper oxide (CuO) NPs, and at different time intervals (3, 14, 42 and 93 days), the composition of cell populations of innate and adaptive immunity was evaluated in the spleen by flow cytometry. The ability of spleen cells from exposed and control mice to respond to stimulation with T- or B-cell mitogens by proliferation and by production of cytokines IL-2, IL-6, IL-10, IL-17 and IFN-γ was characterized. The results showed that the inhalation of CuO NPs predominantly affects the cells of innate immunity (changes in the proportion of eosinophils, neutrophils, macrophages and antigen-presenting cells) with a minimal effect on the percentage of T and B lymphocytes. However, the proliferative and secretory activity of T cells was already significantly enhanced after 3 days from the start of inhalation, decreased on day 14 and normalized at the later time intervals. There was no correlation between the impacts of NPs on the cells of innate and adaptive immunity. The results have shown that the inhalation of CuO NPs significantly alters the composition of cell populations of innate immunity and modulates the proliferation and production of cytokines by cells of the adaptive immune system. However, the immunomodulatory effects of inhaled NPs strongly depend on the time of inhalation.

• Klíčová slova
• CuO nanoparticles, adaptive immunity, immunoreactivity, inhalation, innate immunity,
• MeSH
• adaptivní imunita účinky léků   MeSH
• aplikace inhalační MeSH
• cytokiny biosyntéza   MeSH
• kinetika MeSH
• měď aplikace a dávkování   toxicita   MeSH
• modely u zvířat MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nanočástice toxicita   MeSH
• přirozená imunita účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cupric oxide MeSH Prohlížeč
• cytokiny MeSH
• měď MeSH

Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F2t-isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fibroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2.5 µm for 4 and 24 h. B[a]P and 3-NBA induced expression of PAH metabolising, but not antioxidant enzymes. The concentrations of IsoP decreased, whereas the levels of AA tended to increase. Although the activity of NF-κB was not detected, the tested compounds affected the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The levels of prostaglandin E2 (PGE2) decreased following exposure to B[a]P, whereas 3-NBA exposure tended to increase PGE2 concentration. A distinct response was observed after EOM exposure: expression of PAH-metabolising enzymes was induced, IsoP levels increased after 24-h treatment but AA concentration was not affected. The activity of NF-κB increased after both exposure periods, and a significant induction of PTGS2 expression was found following 4-h treatment. Similarly to PAHs, the EOM exposure was associated with a decrease of PGE2 levels. In summary, exposure to PAHs with low pro-oxidant potential results in a decrease of IsoP levels implying 'antioxidant' properties. For such compounds, IsoP may not be a suitable marker of lipid peroxidation.

• MeSH
• aromatické hydroxylasy metabolismus   MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• dinoprost analogy a deriváty   biosyntéza   metabolismus   MeSH
• dinoproston biosyntéza   metabolismus   MeSH
• fibroblasty účinky léků   enzymologie   MeSH
• kultivované buňky MeSH
• kyselina arachidonová metabolismus   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• NF-kappa B metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• pevné částice toxicita   MeSH
• plíce cytologie   účinky léků   embryologie   enzymologie   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrobenzanthrone MeSH Prohlížeč
• 8-epi-prostaglandin F2alpha MeSH Prohlížeč
• aromatické hydroxylasy MeSH
• benz(a)anthraceny MeSH
• benzopyren MeSH
• cyklooxygenasa 2 MeSH
• dinoprost MeSH
• dinoproston MeSH
• kyselina arachidonová MeSH
• látky znečišťující vzduch MeSH
• NF-kappa B MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• reaktivní formy kyslíku MeSH

Cells grown in monocultures are widely used to model lung tissue. As a result of these culture conditions, these cells exhibit poor morphological similarity to those present in in vivo lung tissue. MucilAir™, a 3-D in vitro model comprising human basal, goblet and ciliated cells, represents a fully differentiated respiratory epithelium that can be used as an alternative and a more realistic system. The aim of our study was to compare the effects of short-term and long-term exposure to two polycyclic aromatic hydrocarbons (PAHs) - benzo[a]pyrene (B[a]P) and 3-nitrobenzanthrone (3-NBA) - using MucilAir as a model of human lung tissue. Two concentrations (0.1 μM and 1 μM) were tested at three time points (24 hours, 7 days and 28 days). Several aspects were assessed: cytotoxicity (lactate dehydrogenase (LDH) release), integrity of the cell layer (transepithelial electrical resistance (TEER)), induction of oxidative stress (reactive oxygen species production) and changes in the expression of selected genes involved in PAH metabolism (CYP1A1 and AKR1C2) and the antioxidant response (ALDH3A1, SOD1, SOD2, GPX1, CAT, HMOX1 and TXNRD1). The results showed that exposure to B[a]P caused a spike in LDH release at day 5. Exposure to 3-NBA caused a number of spikes in LDH release, starting at day 5, and a decrease in TEER after 11 days. CYP1A1 gene expression was upregulated after the 7-day and 28-day B[a]P exposures, as well as after the 24-hour and 7-day 3-NBA exposures. HMOX1 and SOD1 were downregulated after both 24-hour PAH treatments. HMOX1 was upregulated after a 1-week exposure to 3-NBA. There were no significant changes in the messenger RNA (mRNA) levels of AKR1C2, ALDH3A1, TXNRD1, SOD2, GPX1 or CAT. These results illustrate the potential use of this 3-D in vitro lung tissue model in studying the effects of chronic exposure to PAHs.

• Klíčová slova
• 3-D cell culture, 3-nitrobenzanthrone, benzo[a]pyrene, cytotoxicity, gene expression, lung, oxidative stress,
• MeSH
• biologické modely * MeSH
• kultivované buňky * účinky léků   MeSH
• lidé MeSH
• plíce cytologie   účinky léků   MeSH
• polycyklické aromatické uhlovodíky * toxicita   MeSH
• regulace genové exprese účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polycyklické aromatické uhlovodíky * 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

Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.

• Klíčová slova
• Aryl hydrocarbon receptor, Dioxins, Global gene expression profiling, Lung cancer,
• MeSH
• aktivace transkripce účinky léků   MeSH
• azosloučeniny toxicita   MeSH
• benzopyren toxicita   MeSH
• buňky A549 MeSH
• časové faktory MeSH
• fluoreny toxicita   MeSH
• genetická transkripce účinky léků   MeSH
• genové regulační sítě účinky léků   MeSH
• indoly toxicita   MeSH
• karbazoly toxicita   MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• lidé MeSH
• ligandy MeSH
• nádory plic genetika   metabolismus   MeSH
• polychlorované dibenzodioxiny toxicita   MeSH
• pyrazoly toxicita   MeSH
• receptory aromatických uhlovodíků agonisté   metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• signální transdukce účinky léků   MeSH
• stanovení celkové genové exprese metody   MeSH
• thiazoly toxicita   MeSH
• transkripční faktory bHLH agonisté   metabolismus   MeSH
• transkriptom účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester MeSH Prohlížeč
• 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide MeSH Prohlížeč
• 6-formylindolo(3,2-b)carbazole MeSH Prohlížeč
• AHR protein, human MeSH Prohlížeč
• azosloučeniny MeSH
• benzo(k)fluoranthene MeSH Prohlížeč
• benzopyren MeSH
• fluoreny MeSH
• indoly MeSH
• karbazoly MeSH
• látky znečišťující životní prostředí MeSH
• ligandy MeSH
• polychlorované dibenzodioxiny MeSH
• pyrazoly MeSH
• receptory aromatických uhlovodíků MeSH
• thiazoly MeSH
• transkripční faktory bHLH MeSH