TY  - 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 .

TY  - JOUR
AU  - Jovanović Marić, Jovana
AU  - Kolarević, Stoimir
AU  - Đorđević Aleksić, Jelena
AU  - Sunjog, Karolina
AU  - Nikolić, Ivan
AU  - Marić, Ana
AU  - Ilić, Marija
AU  - Simonović, Predrag
AU  - Alygizakis, Nikiforos
AU  - Ng, Kilsey
AU  - Oswald, Petar
AU  - Slobodnik, Jaroslav
AU  - Žegura, Bojana
AU  - Vuković-Gačić, Branka
AU  - Paunović, Momir
AU  - Kračun-Kolarević, Margareta
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2044
AB  - Environmental studies which aim to assess the ecological impact of chemical and other types of pollution should employ a complex weight-of-evidence approach with multiple lines of evidence (LoEs). This study focused on in situ genotoxicological methods such as the comet and micronucleus assays and randomly amplified polymorphic DNA analysis as one of the multiple LoEs (LoE3) on the fish species Alburnus alburnus (bleak) as a bioindicator. The study was carried out within the Joint Danube Survey 4 (JDS4) at nine sites in the Danube River Basin in the Republic of Serbia. Out of nine sampling sites, two were situated at the Tisa, Sava, and Velika Morava rivers, and three sites were at the Danube River. The three additionally employed LoEs were: SumTUwater calculated based on the monitoring data in the database of the Serbian Environmental Protection Agency (SEPA) (LoE1); in vitro analyses of JDS4 water extracts employing genotoxicological methods (LoE2); assessment of the ecological status/potential by SEPA and indication of the ecological status for the sites performed within the JDS4 (LoE4). The analyzed biomarker responses in the bleak were integrated into the unique integrated biomarker response index which was used to rank the sites. The highest pollution pressure was recorded at JDS4 39 and JDS4 36, while the lowest was at JDS4 35. The impact of pollution was confirmed at three sites, JDS4 33, 40, and 41, by all four LoEs. At other sampling sites, a difference was observed regarding the pollution depending on the employed LoEs. This indicates the importance of implementing a comprehensive weight-of-evidence approach to ensure the impact of pollution is not overlooked when using only one LoE as is often the case in environmental studies.
PB  - Oxford University Press
T2  - Mutagenesis
T1  - In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach—the Joint Danube Survey 4 Case Study
EP  - 32
IS  - 1
SP  - 21
VL  - 38
DO  - 10.1093/mutage/geac024
ER  - 

@article{
author = "Jovanović Marić, Jovana and Kolarević, Stoimir and Đorđević Aleksić, Jelena and Sunjog, Karolina and Nikolić, Ivan and Marić, Ana and Ilić, Marija and Simonović, Predrag and Alygizakis, Nikiforos and Ng, Kilsey and Oswald, Petar and Slobodnik, Jaroslav and Žegura, Bojana and Vuković-Gačić, Branka and Paunović, Momir and Kračun-Kolarević, Margareta",
year = "2023",
abstract = "Environmental studies which aim to assess the ecological impact of chemical and other types of pollution should employ a complex weight-of-evidence approach with multiple lines of evidence (LoEs). This study focused on in situ genotoxicological methods such as the comet and micronucleus assays and randomly amplified polymorphic DNA analysis as one of the multiple LoEs (LoE3) on the fish species Alburnus alburnus (bleak) as a bioindicator. The study was carried out within the Joint Danube Survey 4 (JDS4) at nine sites in the Danube River Basin in the Republic of Serbia. Out of nine sampling sites, two were situated at the Tisa, Sava, and Velika Morava rivers, and three sites were at the Danube River. The three additionally employed LoEs were: SumTUwater calculated based on the monitoring data in the database of the Serbian Environmental Protection Agency (SEPA) (LoE1); in vitro analyses of JDS4 water extracts employing genotoxicological methods (LoE2); assessment of the ecological status/potential by SEPA and indication of the ecological status for the sites performed within the JDS4 (LoE4). The analyzed biomarker responses in the bleak were integrated into the unique integrated biomarker response index which was used to rank the sites. The highest pollution pressure was recorded at JDS4 39 and JDS4 36, while the lowest was at JDS4 35. The impact of pollution was confirmed at three sites, JDS4 33, 40, and 41, by all four LoEs. At other sampling sites, a difference was observed regarding the pollution depending on the employed LoEs. This indicates the importance of implementing a comprehensive weight-of-evidence approach to ensure the impact of pollution is not overlooked when using only one LoE as is often the case in environmental studies.",
publisher = "Oxford University Press",
journal = "Mutagenesis",
title = "In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach—the Joint Danube Survey 4 Case Study",
pages = "32-21",
number = "1",
volume = "38",
doi = "10.1093/mutage/geac024"
}

Jovanović Marić, J., Kolarević, S., Đorđević Aleksić, J., Sunjog, K., Nikolić, I., Marić, A., Ilić, M., Simonović, P., Alygizakis, N., Ng, K., Oswald, P., Slobodnik, J., Žegura, B., Vuković-Gačić, B., Paunović, M.,& Kračun-Kolarević, M.. (2023). In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach—the Joint Danube Survey 4 Case Study. in Mutagenesis
Oxford University Press., 38(1), 21-32.
https://doi.org/10.1093/mutage/geac024

Jovanović Marić J, Kolarević S, Đorđević Aleksić J, Sunjog K, Nikolić I, Marić A, Ilić M, Simonović P, Alygizakis N, Ng K, Oswald P, Slobodnik J, Žegura B, Vuković-Gačić B, Paunović M, Kračun-Kolarević M. In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach—the Joint Danube Survey 4 Case Study. in Mutagenesis. 2023;38(1):21-32.
doi:10.1093/mutage/geac024 .

Jovanović Marić, Jovana, Kolarević, Stoimir, Đorđević Aleksić, Jelena, Sunjog, Karolina, Nikolić, Ivan, Marić, Ana, Ilić, Marija, Simonović, Predrag, Alygizakis, Nikiforos, Ng, Kilsey, Oswald, Petar, Slobodnik, Jaroslav, Žegura, Bojana, Vuković-Gačić, Branka, Paunović, Momir, Kračun-Kolarević, Margareta, "In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach—the Joint Danube Survey 4 Case Study" in Mutagenesis, 38, no. 1 (2023):21-32,
https://doi.org/10.1093/mutage/geac024 . .