Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells

Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells

We have previously shown that amifostine differentially modulated the DNA-damaging action of idarubicin in normal and cancer cells and that the presence of p53 protein and oncogenic tyrosine kinases might play a role in this diversity. Aim: To investigate further this effect we have studied the infl...

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Бібліографічні деталі
Дата:2008
Автори: Wozniak, K., Gloc, E., Morawiec, Z., Blasiak, J.
Формат: Стаття
Мова:English
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2008
Назва видання:Experimental Oncology
Теми:
Original contributions
Онлайн доступ:http://dspace.nbuv.gov.ua/handle/123456789/139026
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells / K. Wozniak, E. Gloc, Z. Morawiec, J. Blasiak // Experimental Oncology. — 2008. — Т. 30, № 1. — С. 22–28. — Бібліогр.: 34 назв. — англ.

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spelling irk-123456789-1390262018-06-20T03:05:05Z Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells Wozniak, K. Gloc, E. Morawiec, Z. Blasiak, J. Original contributions We have previously shown that amifostine differentially modulated the DNA-damaging action of idarubicin in normal and cancer cells and that the presence of p53 protein and oncogenic tyrosine kinases might play a role in this diversity. Aim: To investigate further this effect we have studied the influence of amifostine on idarubicin-induced DNA double-strand breaks (DSBs) and apoptosis. Methods: We employed pulse-field gel electrophoresis () for the detection of DSBs and assessment of their repair in human normal lymphocytes and chronic myelogenous leukaemia K562 cells lacking p53 activity and expressing the BCR/ABL tyrosine kinase. Apoptosis was evaluated by caspase-3 activity assay assisted by the alkaline comet assay and DAPI staining. Results: Idarubicin induced DSBs in a dose-independent manner in normal and cancer cells. Both types of the cells did not repair these lesions in 120 min and amifostine differentially modulated their level — decreased it in the lymphocytes and increased in K562 cells. In contrast to control cells, amifostine potentated apoptotic DNA fragmentation, chromatin condensation and the activity of caspase-3 in leukaemia cells. Conclusion: Amifostine can differentially modulate DSBs and apoptosis induced by idarubicin in normal and cancer cells. It can protect normal cells against drug-induced DNA damage and it can potentate the action of the drug in leukaemic cells. Further studies on link between amifostine-induced modulation of DSBs and apoptosis of cancer cells will bring a deeper insight into molecular mechanism of amifostine action. Ранее нами было показано, что амифостин дифференциально модулирует ДНК-повреждающее действие идарубицина в нормальных и злокачественных клетках, и что наличие белка р53 и онкогенных тирозин киназ может иметь значение для этих различий. Цель: изучить влияние амифостина на идарубицин-опосредованные двухнитевые разрывы ДНК (DSBs) и апоптоз. Методы: мы применили гель-электрофорез в пульсирующем поле (PFGE) для выявления DSBs и изучения их репарации в нормальных лимфоцитах человека и клетках K562 хронической миелоидной лейкемии, у которых р53 неактивен и экспрессирована BCR/ABL-тирозин киназа. Апоптоз оценивали с помощью реактивов для выявления активности каспазы-3, проведения щелочного гель-электрофореза одиночных клеток и DAPI-окрашивания. Результаты: идарубицин вызывает образование DSBs в нормальных и злокачественных клетках независимо от дозы. Оба типа клеток не репарировали эти повреждения за 120 мин, при этом амифостин дифференциально молулировал уровень DSBs — уменьшал в лимфоцитах и увеличивал в K562-клетках. В отличие от контрольных клеток амифостин потенциировал апоптическую фрагментацию ДНК, конденсацию хроматина и активность каспазы-3 в лейкемических клетках. Выводы: амифостин может дифференциально модулировать DSBs и апоптоз, вызванные идарубицином в нормальных и злокачественных клетках. Он может защитить нормальные клетки от повреждения ДНК, вызванного химиопрепаратом, и в то же время потенциировать действие препарата на лейкемические клетки. Дальнейшие исследования связи между вызванной амифостином модуляцией DSBs и апоптоза опухолевых клеток позволит лучше понять молекулярные механизмы действия амифостина. 2008 Article Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells / K. Wozniak, E. Gloc, Z. Morawiec, J. Blasiak // Experimental Oncology. — 2008. — Т. 30, № 1. — С. 22–28. — Бібліогр.: 34 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/139026 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Wozniak, K.
Gloc, E.
Morawiec, Z.
Blasiak, J.
Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
Experimental Oncology
description We have previously shown that amifostine differentially modulated the DNA-damaging action of idarubicin in normal and cancer cells and that the presence of p53 protein and oncogenic tyrosine kinases might play a role in this diversity. Aim: To investigate further this effect we have studied the influence of amifostine on idarubicin-induced DNA double-strand breaks (DSBs) and apoptosis. Methods: We employed pulse-field gel electrophoresis () for the detection of DSBs and assessment of their repair in human normal lymphocytes and chronic myelogenous leukaemia K562 cells lacking p53 activity and expressing the BCR/ABL tyrosine kinase. Apoptosis was evaluated by caspase-3 activity assay assisted by the alkaline comet assay and DAPI staining. Results: Idarubicin induced DSBs in a dose-independent manner in normal and cancer cells. Both types of the cells did not repair these lesions in 120 min and amifostine differentially modulated their level — decreased it in the lymphocytes and increased in K562 cells. In contrast to control cells, amifostine potentated apoptotic DNA fragmentation, chromatin condensation and the activity of caspase-3 in leukaemia cells. Conclusion: Amifostine can differentially modulate DSBs and apoptosis induced by idarubicin in normal and cancer cells. It can protect normal cells against drug-induced DNA damage and it can potentate the action of the drug in leukaemic cells. Further studies on link between amifostine-induced modulation of DSBs and apoptosis of cancer cells will bring a deeper insight into molecular mechanism of amifostine action.
format Article
author Wozniak, K.
Gloc, E.
Morawiec, Z.
Blasiak, J.
author_facet Wozniak, K.
Gloc, E.
Morawiec, Z.
Blasiak, J.
author_sort Wozniak, K.
title Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
title_short Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
title_full Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
title_fullStr Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
title_full_unstemmed Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
title_sort amifostine can differentially modulate dna double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2008
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/139026
citation_txt Amifostine can differentially modulate DNA double-strand breaks and apoptosis induced by idarubicin in normal and cancer cells / K. Wozniak, E. Gloc, Z. Morawiec, J. Blasiak // Experimental Oncology. — 2008. — Т. 30, № 1. — С. 22–28. — Бібліогр.: 34 назв. — англ.
series Experimental Oncology
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AT gloce amifostinecandifferentiallymodulatednadoublestrandbreaksandapoptosisinducedbyidarubicininnormalandcancercells
AT morawiecz amifostinecandifferentiallymodulatednadoublestrandbreaksandapoptosisinducedbyidarubicininnormalandcancercells
AT blasiakj amifostinecandifferentiallymodulatednadoublestrandbreaksandapoptosisinducedbyidarubicininnormalandcancercells
first_indexed 2023-10-18T21:19:33Z
last_indexed 2023-10-18T21:19:33Z
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