Number of the records: 1
Differential DNA damage response and cell fate in human lung cells after exposure to genotoxic compounds
- 1.
SYSNO ASEP 0581742 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Differential DNA damage response and cell fate in human lung cells after exposure to genotoxic compounds Author(s) Líbalová, Helena (UEM-P) RID
Závodná, Táňa (UEM-P)
Margaryan, Hasmik (UEM-P)
Milcová, Alena (UEM-P)
Vrbová, Kristýna (UEM-P)
Barošová, Hana (UEM-P)
Červená, Tereza (UEM-P) ORCID, RID
Topinka, Jan (UEM-P) RID, ORCID
Rössner ml., Pavel (UEM-P) RID, ORCIDArticle number 105710 Source Title Toxicology in Vitro. - : Elsevier - ISSN 0887-2333
Roč. 94, feb. (2024)Number of pages 13 s. Language eng - English Country GB - United Kingdom Keywords genotoxicity ; polycyclic aromatic hydrocarbons ; anticancer drugs ; DNA damage response ; cell fate OECD category Public and environmental health R&D Projects GJ18-06548Y GA ČR - Czech Science Foundation (CSF) LM2023066 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2023053 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001821 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GJ18-06548Y GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 001100361700001 EID SCOPUS 85173992366 DOI 10.1016/j.tiv.2023.105710 Annotation 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. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2025 Electronic address https://www.sciencedirect.com/science/article/pii/S0887233323001595?via%3Dihub
Number of the records: 1