Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay
Analiza dnk oštećenja izazvanog tiazofurinom u humanim ćelijama pune krvi primenom in vitro komet testa
Апстракт
Objective. Inosine 5'-monophosphate dehydrogenase (IMPDH) activity in cancer cells is increased. Tiazofurin selectively inhibits the activity of IMPDH, and it has been granted for the treatment of different cancers and new viral diseases. Its widespread use was limited because exposure to tiazofurin under certain circumstances was found to have a higher frequency of severe non-hematologic toxicity. Therefore, the objective of this study was to examine genotoxic action and inducement of DNA damage of tiazofurin using the comet assay. Methods. The ability of tiazofurin to induce DNA damage was evaluated using single-cell gel electrophoresis (SCGE) technique/comet assay. Human whole blood cells were exposed to three final concentrations of tiazofurin (1µM/mL, 2 µM/mL, and 5 µM/mL) for 30 min in vitro. Results. Our results indicate that tiazofurin produced a significant level of DNA damage on whole blood cells after 30 min of exposure vs. control. All tested concentrations were significant...ly comet-forming, in a concentration-dependent manner. Conclusion. Our investigation on the tiazofurin-treated cells and their relationship to the formation of DNA damage demonstrated that the genotoxic effect was induced after exposure to tiazofurin under described conditions.
Cilj. Aktivnost inozin 5’-monofosfat dehidrogenaze
(IMPDH) povećana je u ćelijama karcinoma. Tiazofurin
selektivno inhibira aktivnost IMPDH i odobren je za lečenje
različitih karcinoma i novih virusnih bolesti. Njegova široko
rasprostranjena upotreba bila je ograničena jer je utvrđeno
da je izloženost tiazofurinu pod određenim okolnostima
imala veću incidencu ozbiljne nehematološke toksičnosti.
Stoga je cilj ove studije bio da se pomoću komet testa ispita
genotoksično delovanje i izazivanje DNK oštećenja
tiazofurinom.
Metode. Sposobnost tiazofurina da izazove DNK
oštećenje procenjena je primenom elektroforeze DNK
pojedinačnih ćelija (SCGE) / komet testa. Ćelije pune krvi su
bile izložene trima konačnim koncentracijama tiazofurina (1
µM/mL, 2 µM/mL, and 5 µM/mL) tokom 30 minuta in vitro.
Rezultati. Naši rezultati ukazuju na to da je tiazofurin
proizveo značajan nivo DNK oštećenja na ćelijama pune krvi
nakon 30 minuta izlaganja u odnosu na kontrolu. Sve
ispitiva...ne koncentracije su dovele do značajnog nastanka
kometa, pri čemu je nivo oštećenja rastao s koncentracijom.
Zaključak. Naše istraživanje ćelija tretiranih
tiazofurinom i njihova reakcija na izazivanje DNK oštećenja pokazalo je da je tiazofurin ispoljio genotoksični efekat pod opisanim uslovima
Извор:
Medicinski časopis, 2020, 54, 3, 91-95Издавач:
- Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
- hCOMET COST action (No. 15132)
Колекције
Институција/група
Fakultet veterinarske medicineTY - JOUR AU - Topalović, Dijana AU - Živković, Lada AU - Đelić, Ninoslav AU - Bajić, Vladan AU - Spremo-Potparević, Biljana PY - 2020 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2050 AB - Objective. Inosine 5'-monophosphate dehydrogenase (IMPDH) activity in cancer cells is increased. Tiazofurin selectively inhibits the activity of IMPDH, and it has been granted for the treatment of different cancers and new viral diseases. Its widespread use was limited because exposure to tiazofurin under certain circumstances was found to have a higher frequency of severe non-hematologic toxicity. Therefore, the objective of this study was to examine genotoxic action and inducement of DNA damage of tiazofurin using the comet assay. Methods. The ability of tiazofurin to induce DNA damage was evaluated using single-cell gel electrophoresis (SCGE) technique/comet assay. Human whole blood cells were exposed to three final concentrations of tiazofurin (1µM/mL, 2 µM/mL, and 5 µM/mL) for 30 min in vitro. Results. Our results indicate that tiazofurin produced a significant level of DNA damage on whole blood cells after 30 min of exposure vs. control. All tested concentrations were significantly comet-forming, in a concentration-dependent manner. Conclusion. Our investigation on the tiazofurin-treated cells and their relationship to the formation of DNA damage demonstrated that the genotoxic effect was induced after exposure to tiazofurin under described conditions. AB - Cilj. Aktivnost inozin 5’-monofosfat dehidrogenaze (IMPDH) povećana je u ćelijama karcinoma. Tiazofurin selektivno inhibira aktivnost IMPDH i odobren je za lečenje različitih karcinoma i novih virusnih bolesti. Njegova široko rasprostranjena upotreba bila je ograničena jer je utvrđeno da je izloženost tiazofurinu pod određenim okolnostima imala veću incidencu ozbiljne nehematološke toksičnosti. Stoga je cilj ove studije bio da se pomoću komet testa ispita genotoksično delovanje i izazivanje DNK oštećenja tiazofurinom. Metode. Sposobnost tiazofurina da izazove DNK oštećenje procenjena je primenom elektroforeze DNK pojedinačnih ćelija (SCGE) / komet testa. Ćelije pune krvi su bile izložene trima konačnim koncentracijama tiazofurina (1 µM/mL, 2 µM/mL, and 5 µM/mL) tokom 30 minuta in vitro. Rezultati. Naši rezultati ukazuju na to da je tiazofurin proizveo značajan nivo DNK oštećenja na ćelijama pune krvi nakon 30 minuta izlaganja u odnosu na kontrolu. Sve ispitivane koncentracije su dovele do značajnog nastanka kometa, pri čemu je nivo oštećenja rastao s koncentracijom. Zaključak. Naše istraživanje ćelija tretiranih tiazofurinom i njihova reakcija na izazivanje DNK oštećenja pokazalo je da je tiazofurin ispoljio genotoksični efekat pod opisanim uslovima PB - Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac T2 - Medicinski časopis T1 - Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay T1 - Analiza dnk oštećenja izazvanog tiazofurinom u humanim ćelijama pune krvi primenom in vitro komet testa VL - 54 IS - 3 SP - 91 EP - 95 DO - 10.5937/mckg54-28798 ER -
@article{ author = "Topalović, Dijana and Živković, Lada and Đelić, Ninoslav and Bajić, Vladan and Spremo-Potparević, Biljana", year = "2020", abstract = "Objective. Inosine 5'-monophosphate dehydrogenase (IMPDH) activity in cancer cells is increased. Tiazofurin selectively inhibits the activity of IMPDH, and it has been granted for the treatment of different cancers and new viral diseases. Its widespread use was limited because exposure to tiazofurin under certain circumstances was found to have a higher frequency of severe non-hematologic toxicity. Therefore, the objective of this study was to examine genotoxic action and inducement of DNA damage of tiazofurin using the comet assay. Methods. The ability of tiazofurin to induce DNA damage was evaluated using single-cell gel electrophoresis (SCGE) technique/comet assay. Human whole blood cells were exposed to three final concentrations of tiazofurin (1µM/mL, 2 µM/mL, and 5 µM/mL) for 30 min in vitro. Results. Our results indicate that tiazofurin produced a significant level of DNA damage on whole blood cells after 30 min of exposure vs. control. All tested concentrations were significantly comet-forming, in a concentration-dependent manner. Conclusion. Our investigation on the tiazofurin-treated cells and their relationship to the formation of DNA damage demonstrated that the genotoxic effect was induced after exposure to tiazofurin under described conditions., Cilj. Aktivnost inozin 5’-monofosfat dehidrogenaze (IMPDH) povećana je u ćelijama karcinoma. Tiazofurin selektivno inhibira aktivnost IMPDH i odobren je za lečenje različitih karcinoma i novih virusnih bolesti. Njegova široko rasprostranjena upotreba bila je ograničena jer je utvrđeno da je izloženost tiazofurinu pod određenim okolnostima imala veću incidencu ozbiljne nehematološke toksičnosti. Stoga je cilj ove studije bio da se pomoću komet testa ispita genotoksično delovanje i izazivanje DNK oštećenja tiazofurinom. Metode. Sposobnost tiazofurina da izazove DNK oštećenje procenjena je primenom elektroforeze DNK pojedinačnih ćelija (SCGE) / komet testa. Ćelije pune krvi su bile izložene trima konačnim koncentracijama tiazofurina (1 µM/mL, 2 µM/mL, and 5 µM/mL) tokom 30 minuta in vitro. Rezultati. Naši rezultati ukazuju na to da je tiazofurin proizveo značajan nivo DNK oštećenja na ćelijama pune krvi nakon 30 minuta izlaganja u odnosu na kontrolu. Sve ispitivane koncentracije su dovele do značajnog nastanka kometa, pri čemu je nivo oštećenja rastao s koncentracijom. Zaključak. Naše istraživanje ćelija tretiranih tiazofurinom i njihova reakcija na izazivanje DNK oštećenja pokazalo je da je tiazofurin ispoljio genotoksični efekat pod opisanim uslovima", publisher = "Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac", journal = "Medicinski časopis", title = "Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay, Analiza dnk oštećenja izazvanog tiazofurinom u humanim ćelijama pune krvi primenom in vitro komet testa", volume = "54", number = "3", pages = "91-95", doi = "10.5937/mckg54-28798" }
Topalović, D., Živković, L., Đelić, N., Bajić, V.,& Spremo-Potparević, B.. (2020). Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay. in Medicinski časopis Kragujevac : Srpsko lekarsko društvo - Okružna podružnica Kragujevac., 54(3), 91-95. https://doi.org/10.5937/mckg54-28798
Topalović D, Živković L, Đelić N, Bajić V, Spremo-Potparević B. Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay. in Medicinski časopis. 2020;54(3):91-95. doi:10.5937/mckg54-28798 .
Topalović, Dijana, Živković, Lada, Đelić, Ninoslav, Bajić, Vladan, Spremo-Potparević, Biljana, "Analysis of tiazofurin-induced DNA damage in human whole blood cells using an in vitro comet assay" in Medicinski časopis, 54, no. 3 (2020):91-95, https://doi.org/10.5937/mckg54-28798 . .