Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.

• MeSH
• antigen Ki-67 metabolismus   MeSH
• buněčná diferenciace * genetika   MeSH
• buněčný rodokmen MeSH
• histondemethylasy MeSH
• lidé MeSH
• meduloblastom * klasifikace   genetika   patologie   MeSH
• metencephalon * embryologie   patologie   MeSH
• mozeček embryologie   patologie   MeSH
• mutace MeSH
• nádory mozečku * klasifikace   genetika   patologie   MeSH
• proteiny hedgehog metabolismus   MeSH
• proteiny T-boxu metabolismus   MeSH
• represorové proteiny MeSH
• svalové proteiny MeSH
• transkripční faktory Otx nedostatek   genetika   MeSH
• transkripční faktory PEBP2A genetika   MeSH
• transkripční faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antigen Ki-67 MeSH
• CBFA2T2 myeloid-transforming gene-related protein MeSH Prohlížeč
• CBFA2T3 protein, human MeSH Prohlížeč
• core binding factor alpha MeSH Prohlížeč
• EOMES protein, human MeSH Prohlížeč
• histondemethylasy MeSH
• KDM6A protein, human MeSH Prohlížeč
• OTX2 protein, human MeSH Prohlížeč
• PRDM6 protein, human MeSH Prohlížeč
• proteiny hedgehog MeSH
• proteiny T-boxu MeSH
• represorové proteiny MeSH
• svalové proteiny MeSH
• transkripční faktory Otx MeSH
• transkripční faktory PEBP2A MeSH
• transkripční faktory MeSH

The dentin-enamel junction (DEJ) is the border where two different mineralized structures - enamel and dentin - meet. The protein-rich DEJ, together with the inner enamel region of mature teeth, is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the DEJ and the adjacent enamel organic matrix (EOM). We studied proteomes of the DEJ and EOM of healthy human molars and compared them with dentin and enamel proteomes from the same teeth. These tissues were cut out of tooth sections by laser capture microdissection, proteins were extracted and cleaved by trypsin, then processed by liquid chromatography coupled to tandem mass spectrometry to analyze the proteome profiles of these tissues. This study identified 46 proteins in DEJ and EOM. The proteins identified have a variety of functions, including calcium ion-binding, formation of extracellular matrix, formation of cytoskeleton, cytoskeletal protein binding, cell adhesion, and transport. Collagens were identified as the most dominant proteins. Tissue-specific proteins, such as ameloblastin and amelogenin, were also detected. Our findings reveal new insight into proteomics of DEJ and EOM, highly mineralized tissues that are obviously difficult to analyze.

• Klíčová slova
• dentin, laser capture microdissection, mass spectrometry, proteome,
• MeSH
• chromatografie kapalinová MeSH
• dentin * MeSH
• lidé MeSH
• mikrodisekce MeSH
• moláry * MeSH
• proteiny metabolismus   MeSH
• proteom analýza   MeSH
• proteomika metody   MeSH
• tandemová hmotnostní spektrometrie MeSH
• zubní sklovina * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny MeSH
• proteom MeSH

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• chronická lymfatická leukemie genetika   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• protein BCL2L11 MeSH
• proteiny regulující apoptózu genetika   MeSH
• proteiny T-boxu genetika   MeSH
• protoonkogenní proteiny genetika   MeSH
• serpiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• BANK1 protein, human MeSH Prohlížeč
• BCL2L11 protein, human MeSH Prohlížeč
• CSRNP1 protein, human MeSH Prohlížeč
• EOMES protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• protein BCL2L11 MeSH
• proteiny regulující apoptózu MeSH
• proteiny T-boxu MeSH
• protoonkogenní proteiny MeSH
• serpin B6 MeSH Prohlížeč
• serpiny MeSH

The cellular response to genotoxic treatment depends on the cell line used. Although tumor cell lines are widely used for genotoxicity tests, the interpretation of the results may be potentially hampered by changes in cellular processes caused by malignant transformation. In our study we used normal human embryonic lung fibroblasts (HEL12469 cells) and tested their response to treatment with benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5 µm (PM2.5) collected in two Czech cities differing in levels and sources of air pollution. We analyzed multiple endpoints associated with exposure to polycyclic aromatic hydrocarbons (PAHs) including the levels of bulky DNA adducts and the nucleotide excision repair (NER) response [expression of XPE, XPC and XPA genes on the level of mRNA and proteins, unscheduled DNA synthesis (UDS)]. EOMs were collected in the winter and summer of 2011 in two Czech cities with different levels and sources of air pollution. The effects of the studied compounds were analyzed in the presence (+S9) and absence (-S9) of the rat liver microsomal S9 fraction. The levels of bulky DNA adducts were highest after treatment with B[a]P, followed by winter EOMs; their induction by summer EOMs was weak. The induction of both mRNA and protein expression was observed, with the most pronounced effects after treatment with B[a]P (-S9); the response induced by EOMs from both cities and seasons was substantially weaker. The expression of DNA repair genes was not accompanied by the induction of UDS activity. In summary, our results indicate that the tested compounds induced low levels of DNA damage and affected the expression of NER genes; however, nucleotide excision repair was not induced.

• MeSH
• adukty DNA MeSH
• buněčné linie MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• látky znečišťující vzduch chemie   toxicita   MeSH
• látky znečišťující životní prostředí chemie   toxicita   MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• oprava DNA * MeSH
• pevné částice chemie   toxicita   MeSH
• plíce MeSH
• polycyklické aromatické uhlovodíky chemie   toxicita   MeSH
• proliferace buněk účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• xeroderma pigmentosum - protein skupiny A genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• DNA vazebné proteiny MeSH
• látky znečišťující vzduch MeSH
• látky znečišťující životní prostředí MeSH
• messenger RNA MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• xeroderma pigmentosum - protein skupiny A MeSH
• XPA protein, human MeSH Prohlížeč
• XPC protein, human MeSH Prohlížeč

Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).

• Klíčová slova
• MR1, cytokines, gammadelta T lymphocytes, mucosal associated invariant T cells, psoriasis,
• MeSH
• buněčná diferenciace MeSH
• cytotoxicita imunologická MeSH
• dospělí MeSH
• histokompatibilita - antigeny třídy I metabolismus   MeSH
• krevní oběh MeSH
• lidé středního věku MeSH
• lidé MeSH
• MAIT buňky imunologie   MeSH
• mladý dospělý MeSH
• přirozená imunita MeSH
• protein promyelocytické leukemie s motivem zinkového prstu genetika   metabolismus   MeSH
• psoriáza imunologie   MeSH
• receptory antigenů T-buněk gama-delta metabolismus   MeSH
• T-lymfocyty imunologie   MeSH
• Th1 buňky imunologie   MeSH
• vedlejší histokompatibilní antigeny metabolismus   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
• histokompatibilita - antigeny třídy I MeSH
• MR1 protein, human MeSH Prohlížeč
• protein promyelocytické leukemie s motivem zinkového prstu MeSH
• receptory antigenů T-buněk gama-delta MeSH
• vedlejší histokompatibilní antigeny MeSH

In order to evaluate the ability of a representative polycyclic aromatic hydrocarbon (PAH) and PAH-containing complex mixtures to induce double strand DNA breaks (DSBs) and repair of damaged DNA in human embryonic lung fibroblasts (HEL12469 cells), we investigated the effect of benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5μm (PM2.5) on nonhomologous DNA end joining (NHEJ) and induction of stable chromosome aberrations (CAs). PM2.5 was collected in winter and summer 2011 in two Czech cities differing in levels and sources of air pollutants. The cells were treated for 24h with the following concentrations of tested chemicals: B[a]P: 1μM, 10μM, 25μM; EOMs: 1μg/ml, 10μg/ml, 25μg/ml. We tested several endpoints representing key steps leading from DSBs to the formation of CAs including histone H2AX phosphorylation, levels of proteins Ku70, Ku80 and XRCC4 participating in NHEJ, in vitro ligation activity of nuclear extracts of the HEL12469 cells and the frequency of stable CAs assessed by whole chromosome painting of chromosomes 1, 2, 4, 5, 7 and 17 using fluorescence in situ hybridization. Our results show that 25μM of B[a]P and most of the tested doses of EOMs induced DSBs as indicated by H2AX phosphorylation. DNA damage was accompanied by induction of XRCC4 expression and an increased frequency of CAs. Translocations most frequently affected chromosome 7. We observed only a weak induction of Ku70/80 expression as well as ligation activity of nuclear extracts. In summary, our data suggest the induction of DSBs and NHEJ after treatment of human embryonic lung fibroblasts with B[a]P and complex mixtures containing PAHs.

• Klíčová slova
• Benzo[a]pyrene, Chromosome aberrations, Double-strand DNA breaks, Extractable organic matter, Nonhomologous DNA end joining repair,
• MeSH
• antigen Ku MeSH
• antigeny jaderné genetika   metabolismus   MeSH
• benzopyren toxicita   MeSH
• buněčné linie MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• embryo savčí metabolismus   patologie   MeSH
• fibroblasty metabolismus   patologie   MeSH
• fosforylace účinky léků   genetika   MeSH
• histony genetika   metabolismus   MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• lidé MeSH
• lidské chromozomy genetika   metabolismus   MeSH
• obnova měst MeSH
• oprava DNA spojením konců účinky léků   genetika   MeSH
• pevné částice MeSH
• plíce metabolismus   patologie   MeSH
• translokace genetická účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigen Ku MeSH
• antigeny jaderné MeSH
• benzopyren MeSH
• DNA vazebné proteiny MeSH
• H2AX protein, human MeSH Prohlížeč
• histony MeSH
• látky znečišťující životní prostředí MeSH
• pevné částice MeSH
• XRCC4 protein, human MeSH Prohlížeč
• Xrcc6 protein, human MeSH Prohlížeč

The aim of this study was to investigate the genotoxic effect of single carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), as well as their binary and artificial mixtures containing c-PAHs in the same relative proportions as real complex mixtures, and to investigate the genotoxic effect of environmental mixtures such as EOM (extractable organic matter adsorbed to respirable air particles). We used normal human diploid lung fibroblasts (HEL) in a confluent ("quiescent") state as being closer to in vivo conditions. We determined DNA adducts by (32)P -postlabelling and the expression of p53 and p21(WAF1) proteins by Western blotting. Our results showed that the DNA binding potencies of c-PAHs in quiescent HEL cells were as follows: DB[al]P>>B[a]P>>B[b]F approximately CHRY approximately B[k]F approximately B[a]A approximately DB[ah]A approximately I[cd]P > B[ghi]P. Both DB[al]P and B[a]P were chosen to assess the genotoxic effect of other c-PAHs when present in binary mixtures. In all cases, co-treatment resulted in significantly lower DNA adduct levels as compared with adduct levels resulting from single compounds. The highest inhibitory effect was found in the presence of DB[ah]A followed by B[k]F. In both artificial and EOM mixtures a strong inhibitory effect of other compounds was observed. BPDE-adduct levels were up to five-fold lower in an artificial c-PAH mixture and up to 10-fold lower in an EOM sample than expected from applying B[a]P alone at the same concentration. These results suggest a competition for the metabolic activation enzymes, their saturation and/or inactivation by PAH metabolites. We did not observe the decrease of DNA adducts and induced levels of both p53 and p21(WAF1) proteins during the post-treatment period up to 6 days following exposure. We suggest that parent c-PAHs accumulate inside cells and that they are further activated by newly synthesised enzymes during the post-treatment period. Therefore, unaltered c-PAHs may act as a reservoir inside the cells for the long-term production of active metabolites. The total DNA adduct levels induced in HEL cells after exposure to EOM were generally low as compared with exposure to B[a]P alone under the same conditions. Human diploid lung fibroblasts possess low metabolic capacity than other human target cells. Therefore, it may be easier to competitively inhibit the metabolising enzymes in this cell system. We hypothesise that this finding might explain the generally low PAH-DNA adduct levels detected in human studies using surrogate cells such as blood WBC or lymphocytes that also possess low metabolic capacity.

• MeSH
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid analýza   MeSH
• adukty DNA analýza   účinky léků   MeSH
• benzopyren toxicita   MeSH
• časové faktory MeSH
• diploidie MeSH
• DNA účinky léků   izolace a purifikace   metabolismus   MeSH
• fibroblasty cytologie   účinky léků   metabolismus   MeSH
• karcinogeny životního prostředí toxicita   MeSH
• kultivované buňky MeSH
• lidé MeSH
• plíce cytologie   embryologie   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• vystavení vlivu životního prostředí MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA MeSH
• benzopyren MeSH
• DNA MeSH
• karcinogeny životního prostředí MeSH
• polycyklické aromatické uhlovodíky MeSH

The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.

• Klíčová slova
• Aryl hydrocarbon receptor, Extractable organic matter, Lipid peroxidation, Polycyclic aromatic hydrocarbons,
• MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• buňky A549 MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cytochrom P-450 CYP1A1 metabolismus   MeSH
• lidé MeSH
• mutageny toxicita   MeSH
• nádorové buněčné linie MeSH
• NF-kappa B metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• pevné částice toxicita   MeSH
• pneumocyty účinky léků   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• receptory aromatických uhlovodíků metabolismus   MeSH
• transkripční faktory bHLH metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrobenzanthrone MeSH Prohlížeč
• AHR protein, human MeSH Prohlížeč
• benz(a)anthraceny MeSH
• benzopyren MeSH
• cyklooxygenasa 1 MeSH
• cytochrom P-450 CYP1A1 MeSH
• mutageny MeSH
• NF-kappa B MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• receptory aromatických uhlovodíků MeSH
• transkripční faktory bHLH 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

Heat shock proteins (hsp) are a highly conserved group of proteins that are synthesized as a response to different forms of stress (heat, toxic chemicals, diseases, non-physiological pH changes). Because of their high sensitivity to changes in the environment, these proteins were suggested as possible early biomarkers of exposure in ecotoxicological studies. The purpose of the present study was to check the suitability of hsp 32 and hsp70 as biomarkers of in vitro exposure to environmentally relevant carcinogens: polycyclic aromatic hydrocarbons (PAHs), their nitro-derivates, aromatic amines, acrylonitrile (ACN) and the mixture of organic compounds adsorbed onto ambient airborne particles (extractable organic matter, EOM). The expression of hsp 32 and hsp70 was studied in human diploid lung fibroblasts (HEL cells) and human monocytic leukaemia cells (THP-1 cells) incubated in vitro with different concentrations of dibenzo[a,l]pyrene (DB[a,l]P), 1-nitropyrene, (NP), 4-aminobiphenyl (ABP), ACN and EOM for different periods of time. The incubation of cells with DB[a,l]P, NP, ABP and EOM did not result in increased levels of hsp 32 or hsp70, either in dose- or time-dependent manner. ACN induced the expression of hsp 32 as well as hsp70 in HEL and THP-1 cells, which probably reflects its ability to induce oxidative stress. We conclude that hsp 32 and hsp70 are not suitable biomarkers of an early exposure to PAHs, their nitro-derivates, aromatic amines or EOM under the conditions used.

• MeSH
• akrylonitril chemie   farmakologie   MeSH
• biologické markery analýza   MeSH
• ELISA MeSH
• fibroblasty cytologie   MeSH
• hemová oxygenasa (decyklizující) MeSH
• karcinogeny životního prostředí chemie   farmakologie   MeSH
• kultivované buňky MeSH
• lékové interakce MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• oxidační stres účinky léků   MeSH
• oxygenasy * MeSH
• plíce cytologie   embryologie   MeSH
• proteiny tepelného šoku HSP70 analýza   biosyntéza   MeSH
• proteiny tepelného šoku analýza   biosyntéza   MeSH
• velikost částic MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylonitril MeSH
• biologické markery MeSH
• hemová oxygenasa (decyklizující) MeSH
• Hmox1 protein, rat MeSH Prohlížeč
• karcinogeny životního prostředí MeSH
• oxygenasy * MeSH
• proteiny tepelného šoku HSP70 MeSH
• proteiny tepelného šoku MeSH