Differential DNA damage response and cell fate in human lung cells after exposure to genotoxic compounds

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00581742" target="_blank" >RIV/68378041:_____/24:00581742 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0887233323001595?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0887233323001595?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tiv.2023.105710" target="_blank" >10.1016/j.tiv.2023.105710</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Differential DNA damage response and cell fate in human lung cells after exposure to genotoxic compounds

Popis výsledku v původním jazyce

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. Poly-cyclic 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.

Název v anglickém jazyce

Differential DNA damage response and cell fate in human lung cells after exposure to genotoxic compounds

Popis výsledku anglicky

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. Poly-cyclic 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30304 - Public and environmental health

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology in Vitro

ISSN

0887-2333

e-ISSN

1879-3177

Svazek periodika

94

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

105710

Kód UT WoS článku

001100361700001

EID výsledku v databázi Scopus

2-s2.0-85173992366