Cell cycle perturbations following DNA damage in the presence of ADP-ribosylation inhibitors.

Cell cycle perturbations following DNA damage in the presence of ADP-ribosylation inhibitors.
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ADP-核糖基化抑制剂存在下 DNA 损伤后的细胞周期扰动。

DOI:
10.1093/carcin/6.5.711
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发表时间:
1985
期刊:
影响因子:
4.7
通讯作者:
Measel,J
Measel,J
中科院分区:
医学2区
文献类型:
--
作者:
Jacobson,EL;Meadows,R;Measel,J

文献摘要

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应用流式细胞荧光技术和自显影技术研究了ADP核糖基化反应的有效抑制剂3-甲氧基苯甲酰胺(MBA)对N-甲基-N′-硝基-N-亚硝基胍(MNNG)处理的C3 H 10 T1/2细胞周期进程的影响。在6.8 μM MNNG作用下,MBA使S期从6.5 h延长至10 h,并使细胞聚集在G2期,有丝分裂延迟12 h。进入下一个S期的速度慢5-10倍,细胞最终积累在G2期。增加MNNG的剂量导致在ADP核糖基化不存在的情况下细胞分裂的完全阻断。这些结果表明,ADP-核糖基化反应,这似乎是不必要的DNA切除修复在nondividing细胞,是必不可少的协调事件的DNA切除修复与DNA复制和事件相关的进展,通过细胞周期。
Cell cycle analysis by DNA flow cytofluorimetry and auto-radiography has been utilized to investigate the effects of 3-methoxybenzamlde (MBA), a potent inhibitor of ADP ribosylation reactions, on cell cycle progression in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-treated C3H10T1/2 cells. Following a dose of 6.8 μM MNNG, the presence of MBA resulted in an increased length of S phase from ∽6.5 h to 10 h and in an accumulation of cells in G2with a mitosis delay of 12 h. Progression to the next S phase occurred 5–10 times more slowly and the cells ultimately accumulated in G2Increasing the dose of MNNG resulted in a complete block in cell division in the absence of ADP ribosylation. These results suggest that ADP-ribosylation reactions, which do not seem to be necessary for DNA excision repair in nondividing cells, are essential for co-ordinating the events of DNA excision repair with DNA replication and events related to progression through the cell cycle.