Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives.
Аутори
Đorđević Aleksić, JelenaKolarević, Stoimir
Jovanović Marić, Jovana
Novaković, Irena
Žegura, Bojana
Vuković-Gačić, Branka
Конференцијски прилог (Објављена верзија)
,
Serbian Society of Toxicology
Метаподаци
Приказ свих података о документуАпстракт
2-tert-butyl-1,4-benzoquinone (TBQ) and its alkylthio and arylthio derivatives: 2-tert-butyl-5-(isopropylthio)-1,4-ben- zoquinone, 2-tert-butyl-5-(propylthio)-1,4-benzoquinone, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone, 2-tert-butyl-5-(phenylthio)-1,4-benzoquinone and 2-tert-butyl-6-(phenylthio)-1,4-benzoquinone were synthe- sized as analogs of biologically active compounds of natural origin with antitumor activity: quinone avarol/avarone.
The γH2AX test was used to detect the potential genotoxic effect of TBQ and its derivatives in the HepG2 cell line. In addition, the effect of these substances on the cell cycle was monitored on the same HepG2 model system. Since the phosphorylation of histone H2AX is an early event in the cellular response to DNA double-strand breaks (DSBs), an assay based on the detection of phosphorylated histone H2AX (γH2AX) can be used as a biomarker of genotoxicity and genomic instability. In this work, the γH2AX test and flow cytometry were used to a...nalyze the genotoxic potential and the effect on the cell cycle of TBQ and its derivatives.
Double-strand breaks (DSBs) in DNA are detected with γH2AX-specific antibodies, and the cell cycle in the HepG2 cell line is analyzed by flow cytometry. Based on the obtained results, only 2-tert-butyl-5,6- (ethylenedithio)-1,4-benzoquinone induced increased formation of DSBs.
Also, the same derivative caused a significantly greater arrest of cells in the G2/M phase of the cell cycle compared to TBQ from about 27% (TBQ) to 34% of the total population with a decrease in the S phase cell population. By forming DSBs, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone leads to genomic instability of the HepG2 cell line, which results in cell cycle arrest in the G2/M phase.
Кључне речи:
TBQ / γH2AX assay / DSBs / cell cycleИзвор:
International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia, 2023, 137-138Издавач:
- Serbian Society of Toxicology
Институција/група
Institut za multidisciplinarna istraživanjaTY - CONF AU - Đorđević Aleksić, Jelena AU - Kolarević, Stoimir AU - Jovanović Marić, Jovana AU - Novaković, Irena AU - Žegura, Bojana AU - Vuković-Gačić, Branka PY - 2023 UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/2174 AB - 2-tert-butyl-1,4-benzoquinone (TBQ) and its alkylthio and arylthio derivatives: 2-tert-butyl-5-(isopropylthio)-1,4-ben- zoquinone, 2-tert-butyl-5-(propylthio)-1,4-benzoquinone, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone, 2-tert-butyl-5-(phenylthio)-1,4-benzoquinone and 2-tert-butyl-6-(phenylthio)-1,4-benzoquinone were synthe- sized as analogs of biologically active compounds of natural origin with antitumor activity: quinone avarol/avarone. The γH2AX test was used to detect the potential genotoxic effect of TBQ and its derivatives in the HepG2 cell line. In addition, the effect of these substances on the cell cycle was monitored on the same HepG2 model system. Since the phosphorylation of histone H2AX is an early event in the cellular response to DNA double-strand breaks (DSBs), an assay based on the detection of phosphorylated histone H2AX (γH2AX) can be used as a biomarker of genotoxicity and genomic instability. In this work, the γH2AX test and flow cytometry were used to analyze the genotoxic potential and the effect on the cell cycle of TBQ and its derivatives. Double-strand breaks (DSBs) in DNA are detected with γH2AX-specific antibodies, and the cell cycle in the HepG2 cell line is analyzed by flow cytometry. Based on the obtained results, only 2-tert-butyl-5,6- (ethylenedithio)-1,4-benzoquinone induced increased formation of DSBs. Also, the same derivative caused a significantly greater arrest of cells in the G2/M phase of the cell cycle compared to TBQ from about 27% (TBQ) to 34% of the total population with a decrease in the S phase cell population. By forming DSBs, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone leads to genomic instability of the HepG2 cell line, which results in cell cycle arrest in the G2/M phase. PB - Serbian Society of Toxicology C3 - International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia T1 - Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives. EP - 138 SP - 137 UR - https://hdl.handle.net/21.15107/rcub_rimsi_2174 ER -
@conference{ author = "Đorđević Aleksić, Jelena and Kolarević, Stoimir and Jovanović Marić, Jovana and Novaković, Irena and Žegura, Bojana and Vuković-Gačić, Branka", year = "2023", abstract = "2-tert-butyl-1,4-benzoquinone (TBQ) and its alkylthio and arylthio derivatives: 2-tert-butyl-5-(isopropylthio)-1,4-ben- zoquinone, 2-tert-butyl-5-(propylthio)-1,4-benzoquinone, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone, 2-tert-butyl-5-(phenylthio)-1,4-benzoquinone and 2-tert-butyl-6-(phenylthio)-1,4-benzoquinone were synthe- sized as analogs of biologically active compounds of natural origin with antitumor activity: quinone avarol/avarone. The γH2AX test was used to detect the potential genotoxic effect of TBQ and its derivatives in the HepG2 cell line. In addition, the effect of these substances on the cell cycle was monitored on the same HepG2 model system. Since the phosphorylation of histone H2AX is an early event in the cellular response to DNA double-strand breaks (DSBs), an assay based on the detection of phosphorylated histone H2AX (γH2AX) can be used as a biomarker of genotoxicity and genomic instability. In this work, the γH2AX test and flow cytometry were used to analyze the genotoxic potential and the effect on the cell cycle of TBQ and its derivatives. Double-strand breaks (DSBs) in DNA are detected with γH2AX-specific antibodies, and the cell cycle in the HepG2 cell line is analyzed by flow cytometry. Based on the obtained results, only 2-tert-butyl-5,6- (ethylenedithio)-1,4-benzoquinone induced increased formation of DSBs. Also, the same derivative caused a significantly greater arrest of cells in the G2/M phase of the cell cycle compared to TBQ from about 27% (TBQ) to 34% of the total population with a decrease in the S phase cell population. By forming DSBs, 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone leads to genomic instability of the HepG2 cell line, which results in cell cycle arrest in the G2/M phase.", publisher = "Serbian Society of Toxicology", journal = "International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia", title = "Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives.", pages = "138-137", url = "https://hdl.handle.net/21.15107/rcub_rimsi_2174" }
Đorđević Aleksić, J., Kolarević, S., Jovanović Marić, J., Novaković, I., Žegura, B.,& Vuković-Gačić, B.. (2023). Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives.. in International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia Serbian Society of Toxicology., 137-138. https://hdl.handle.net/21.15107/rcub_rimsi_2174
Đorđević Aleksić J, Kolarević S, Jovanović Marić J, Novaković I, Žegura B, Vuković-Gačić B. Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives.. in International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia. 2023;:137-138. https://hdl.handle.net/21.15107/rcub_rimsi_2174 .
Đorđević Aleksić, Jelena, Kolarević, Stoimir, Jovanović Marić, Jovana, Novaković, Irena, Žegura, Bojana, Vuković-Gačić, Branka, "Detection of double-strand breaks in DNA molecules by the γH2AX assay and analysis of the cell cycle after treatment with potential antitumor agents TBQ and its alkylthio and arylthio derivatives." in International Congress of the Serbian Society of Toxicology & 1. TOXSEE Regional Conference, Belgrade, Serbia (2023):137-138, https://hdl.handle.net/21.15107/rcub_rimsi_2174 .