کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10823545 1061895 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Repair of idarubicin-induced DNA damage: A cause of resistance?
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Repair of idarubicin-induced DNA damage: A cause of resistance?
چکیده انگلیسی
Idarubicin, a widely used anticancer drug inhibits topoisomerase (topo) IIα and induces DNA double strand breaks. The finding that idarubicin-induced DNA damage is repaired before cell death is initiated encouraged us to examine the role of DNA repair for the cytotoxicity of idarubicin in human promyelocytic HL60 leukaemia cells. We found that DNA double strand breaks induced by a 90 min transient exposure to 0.5 μg ml−1 idarubicin were rapidly repaired throughout the whole population, while topo IIα itself was degraded. In spite of DNA repair, the vast majority of cells died within 40 h. Using differential staining of the chromatids and microscopic evaluation of DNA break points, we found evidence for a high number of false ligations of loose DNA strands arising from the inhibition of topo IIα action by idarubicin. If mainly actively transcribed genes are affected, this results in a disruption of vital genetic information, of regulatory sequences and, ultimately, in induction of the cell death pathway. Our results confirm the hypothesis that misrepair of DNA damage is a decisive event in idarubicin-induced cell death. They are discussed in the context of topo IIα-function and the currently known mechanisms of DNA double strand break repair.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 6, Issue 11, 1 November 2007, Pages 1618-1628
نویسندگان
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