DNA damage can impair normal cellular functions and result in various pathophysiological processes including cardiovascular diseases and cancer. We compared the genotoxic potential of diverse DNA damaging agents, and focused on their effects on the DNA damage response (DDR) and cell fate in human lung cells BEAS-2B. Polycyclic aromatic hydrocarbons [PAHs; benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP)] induced DNA strand breaks and oxidative damage to DNA; anticancer drugs doxorubicin (DOX) and 5-bromo-2'-deoxyuridine (BrdU) were less effective. DOX triggered the most robust p53 signaling indicating activation of DDR, followed by cell cycle arrest in the G2/M phase, induction of apoptosis and senescence, possibly due to the severe and irreparable DNA lesions. BrdU not only activated p53, but also increased the percentage of G1-phased cells and caused a massive accumulation of senescent cells. In contrast, regardless the activation of p53, both PAHs did not substantially affect the cell cycle distribution or senescence. Finally, a small fraction of cells accumulated only in the G2/M phase and exhibited increased cell death after the prolonged incubation with B[a]P. Overall, we characterized differential responses to diverse DNA damaging agents resulting in specific cell fate and highlighted the key role of DNA lesion type and the p53 signaling persistence.
TiO2 along with nano-TiO2 are commonly found in consumer products. In vivo studies have observed an accumulation of nano-TiO2 in macrophages. However, characteristics of nano-TiO2 determining toxicity remain unclear. In our study, the cytotoxic effects of 14 diverse nano-TiO2 on THP-1 macrophage-like cells were measured by 3 cytotoxicity assays (MTS, WST-1 and LDH). Total averaged cytotoxicity was calculated using principal component analysis. Characteristics of all 14 nano-TiO2 included hydrodynamic diameter, zeta potential, shape, polydispersity index (PDI) and concentration; moreover, crystal form, specific surface area and crystallite size were measured for 10 nano-TiO2.The variables affecting cytotoxicity were chosen using LASSO (least absolute shrinkage and selection operator). Except for concentration, PDI in media measured within 1 h after preparation of the nanomaterial dispersion was selected as a variable affecting cytotoxicity: stable dispersion resulted in higher cytotoxic effects. Crystallite size has been shown to have nonlinear effects (particles of sizes between 20 and 60 nm were cytotoxic while smaller and larger ones were not) and thus it has been excluded from LASSO. The shape (particles/fibre) and crystal form did not affect the cytotoxicity. PDI and the nonlinear effect of size could be an explanation for the inconsistencies of the cytotoxicity of nano-TiO2 in various studies.
- MeSH
- endotoxiny analýza MeSH
- kultivační média MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- nanočástice chemie toxicita MeSH
- povrchové vlastnosti MeSH
- THP-1 buňky MeSH
- titan chemie toxicita MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chromozomální aberace MeSH
- dospělí MeSH
- financování organizované MeSH
- hodnocení rizik MeSH
- lidé MeSH
- lymfocyty MeSH
- nádory žaludku genetika MeSH
- nádory etiologie genetika MeSH
- registrace statistika a číselné údaje MeSH
- retrospektivní studie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- azbestóza škodlivé účinky MeSH
- biologické markery MeSH
- chromozomální aberace MeSH
- finanční podpora výzkumu jako téma MeSH
- kyselina askorbová aplikace a dávkování MeSH
- lidé MeSH
- pracovní expozice škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- elektrárny MeSH
- ELISA MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- lymfocyty mikrobiologie MeSH
- nádorový supresorový protein p53 biosyntéza MeSH
- pracovní expozice MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- chromozomální aberace MeSH
- cytogenetické vyšetření MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- lymfocyty účinky záření MeSH
- mladiství MeSH
- monitorování životního prostředí metody MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- životní styl MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Geografické názvy
- Česká republika MeSH
