کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9909131 | 1548436 | 2005 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The cell cycle phases of DNA damage and repair initiated by topoisomerase II-targeting chemotherapeutic drugs
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کلمات کلیدی
ssDNAtype II topoisomerasedouble-strand DNATopoisomerase IIzVADSSBTdTCENdsDNADSBSingle-strand DNA - DNA تک رشته ایz-VAD-fmk - Z-VAD-FMKDNA damage - آسیبDNAAcridine orange - آکاردین نارنجیDNA repair - ترمیم DNAterminal deoxynucleotidyl transferase - ترمینال deoxynucleotidyl transferaseDNA strand breaks - رشته DNA شکسته می شودdouble-strand break - شکست دو ردیفsingle-strand break - شکستن تک رشتهStrand breakage - شکستن رشتهCoefficient of Variation - ضریب تغییرCell cycle - چرخه سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Although cytostasis and cytotoxicity induced by cancer chemotherapy drugs targeting topoisomerase II (topoII) arise in specific cell cycle phases, it is unknown whether the drug-initiated DNA damage triggering these responses, or the repair (reversal) of this damage, differs between cell cycle phases or between drug classes. Accordingly, we used a flow cytometric alkaline unwinding assay to measure DNA damage (strand breakage (SB)) and SB repair in each cell cycle compartment of human cancer cell lines treated with clinically relevant concentrations of doxorubicin, daunomycin, etoposide, and mitoxantrone. We found that treated HeLa and A549 cells exhibited the greatest SB in G2/M phase, the least in G1 phase, and generally an intermediate amount in S phase. The cell cycle phase specificity of the DNA damage appeared to be predictive of the cell cycle phase of growth arrest. Furthermore, it appeared to be dependent on topoIIα expression as the extent of SB did not differ between cell cycle compartments in topoIIα-diminished A549(VP)28 cells. HeLa cells were apparently unable to repair doxorubicin-initiated SB. The rate of repair of etoposide-initiated SB in HeLa cells and of mitoxantrone-initiated SB in HeLa and A549 cells was similar in each cell cycle compartment. In A549 cells, the rate of repair of doxorubicin and etoposide-initiated SB differed between cell cycle phases. Overall, these results indicate that the cell cycle phase specificity of cytostasis and cytotoxicity induced in tumor cells by topoII-targeting drugs may be directly related to the cell cycle phase specificity of the drug-initiated DNA damage. Analysis by cell cycle compartment appears to clarify some of the intercellular heterogeneity in the extent of drug-initiated DNA damage and cytotoxicity previously observed in cancer cells analyzed as a single population; this approach might be useful in resolving inconsistent results reported in investigations of tumor cell topoII content versus response to topoII-targeting drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 572, Issues 1â2, 2 May 2005, Pages 27-44
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 572, Issues 1â2, 2 May 2005, Pages 27-44
نویسندگان
Alan J. Potter, Peter S. Rabinovitch,