This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge.

• MeSH
• apoptóza účinky léků   genetika   MeSH
• exprese genu účinky léků   genetika   MeSH
• extracelulární matrix genetika   MeSH
• fibroblasty účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• metylace DNA účinky léků   genetika   MeSH
• mikro RNA genetika   MeSH
• nádory genetika   MeSH
• oxidační stres účinky léků   genetika   MeSH
• plíce účinky léků   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• signální transdukce účinky léků   genetika   MeSH
• stanovení celkové genové exprese metody   MeSH
• uhlík farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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.

• MeSH
• biologické markery MeSH
• biologické modely * 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