1-beta-D-Arabinofuranosylcytosine is Cytotoxic in Quiescent Normal Lymphocytes Undergoing DNA Excision Repair
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概要
- 論文の詳細を見る
We have sought to clarify the potential activity of S-phase specific antileukemic agent 1--D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay. When normal lymphocytes were treated with ultraviolet C or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the processes of DNA excision repair were promptly initiated and rapidly completed. When the cells were incubated with ara-C prior to irradiation or BCNU treatment, the steps of DNA synthesis and rejoining in the repair processes were both inhibited. ara-C-mediated inhibition of the repair processes was concentration-dependent, with the effect peaking at 10 μM. ara-C combined with these DNA repair initiators exerted the subsequent cytotoxicity, which was proportional to the extent of the repair inhibition in the presence of ara-C. In conclusion, ara-C was cytotoxic in quiescent cells undergoing DNA repair. This might be attributed to unrepaired DNA damage that remained in the cells thereby inducing lethal cytotoxicity. Or, alternatively, ara-C might exert its own cytotoxicity by inhibiting DNA synthesis in the repair processes. Such a strategy may be effective against a dormant subpopulation in acute leukemia that survives the chemotherapy.
- Japanese Cancer Associationの論文
- 2002-12-30
著者
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UEDA Takanori
First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui
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Ueda Takanori
福井大学 血液腫瘍内科学
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Ueda T
Department Of Hematology And Oncology University Of Fukui
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Ueda T
Department Of Urology Chiba Cancer Center
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Ueda Takanori
First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui
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Ueda T
First Department Of Internal Medicine University Of Fukui
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Kuraishi Yasunobu
国立金沢病院
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Kuraishi Yasunobu
Idarubicin Study Group Internal Medicine Iii Jikei University School Of Medicine
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Yamauchi T
Department Of Hematology And Oncology University Of Fukui
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Yamauchi Takahiro
福井大学 血液腫瘍内科学
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YAMAUCHI Takahiro
First Department of Internal Medicine, University of Fukui
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KAWAI Yasukazu
First Department of Internal Medicine, Fukui Medical University
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Ueda T
First Department Of Internal Medicine Fukui Medical School
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Ueda Takahiro
First Department Of Internal Medicine Fukui Medical University Idarubicin Study Group
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Kawai Yasukazu
Department Of Hematology And Oncology University Of Fukui
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Kawai Yasukazu
First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui
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Yamauchi Takahiro
First Department Of Internal Medicine Fukui Medical University
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Ueda Takeshi
Department Of Urology Chiba University Graduate School Of Medicine
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