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在存在ADP-核糖基化抑制剂的情况下,DNA损伤后细胞周期的扰动。

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

作者信息

Jacobson E L, Meadows R, Measel J

出版信息

Carcinogenesis. 1985 May;6(5):711-4. doi: 10.1093/carcin/6.5.711.

DOI:10.1093/carcin/6.5.711
PMID:2988807
Abstract

Cell cycle analysis by DNA flow cytofluorimetry and autoradiography has been utilized to investigate the effects of 3-methoxybenzamide (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 microM MNNG, the presence of MBA resulted in an increased length of S phase from approximately 6.5 h to 10 h and in an accumulation of cells in G2 with a mitosis delay of 12 h. Progression to the next S phase occurred 5-10 times more slowly and the cells ultimately accumulated in G2. Increasing 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 coordinating the events of DNA excision repair with DNA replication and events related to progression through the cell cycle.

摘要

通过DNA流式细胞荧光术和放射自显影进行细胞周期分析,已被用于研究3-甲氧基苯甲酰胺(MBA)(一种有效的ADP-核糖基化反应抑制剂)对经N-甲基-N'-硝基-N-亚硝基胍(MNNG)处理的C3H10T1/2细胞的细胞周期进程的影响。给予6.8微摩尔MNNG后,MBA的存在导致S期长度从约6.5小时增加到10小时,并使细胞在G2期积累,有丝分裂延迟12小时。进入下一个S期的进程发生速度慢5至10倍,细胞最终在G2期积累。增加MNNG剂量导致在没有ADP-核糖基化的情况下细胞分裂完全受阻。这些结果表明,ADP-核糖基化反应对于非分裂细胞中的DNA切除修复似乎不是必需的,但对于协调DNA切除修复与DNA复制以及与细胞周期进程相关的事件至关重要。

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