Wojewódzka M, Kruszewski M, Sochanowicz B, Szumiel I
Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Dorodna 16, PL-03-195 Warsaw, Poland.
Int J Radiat Biol. 2004 Jul;80(7):473-82. doi: 10.1080/09553000410001724216.
To investigate the role of poly(ADP-ribosylation) in DNA double-strand break repair and fixation in murine lymphoma L5178Y (LY) sublines, LY-R and LY-S, and a pair of Chinese hamster ovary lines: wild-type and mutant xrs6 cells, that have differences in repair competence and degree of radiosensitization with poly(ADP-ribosylation) inhibitors.
Cells (asynchronous, logarithmic phase) were pre-incubated with 2 mM aminobenzamide at 37 or 25 degrees C, X-irradiated with 10 Gy and allowed to repair DNA breaks for 15, 60 and 120 min at 37 or 25 degrees C. The remaining double-strand break were estimated by the neutral comet assay.
At 37 degrees C, no effect of AB treatment on the repair kinetics was observed either in xrs6 or Chinese hamster ovary (wild-type) cells. In contrast, aminobenzamide decreased the repair of double-strand break in the LY-S line but not the LY-R line, in agreement with the previously observed radiosensitization of LY cells by poly(ADP-ribosylation) inhibition. However, double-strand break rejoining in the repair competent cell lines, Chinese hamster ovary and LY-R, also was affected by aminobenzamide when the post-irradiation incubation was carried out at 25 degrees C. Analysis of these results together with earlier data on LY-S cells have been interpreted in terms of Radford's model of radiation damage fixation.
The reported results indicate that poly(ADP-ribosylation) can be an important modulator of the conversion of DNA damage to lethal events.
研究多聚（ADP-核糖基化）在小鼠淋巴瘤L5178Y（LY）亚系LY-R和LY-S以及一对中国仓鼠卵巢细胞系（野生型和突变型xrs6细胞）的DNA双链断裂修复和固定中的作用，这些细胞系在修复能力以及多聚（ADP-核糖基化）抑制剂的放射增敏程度上存在差异。
将处于对数生长期的异步细胞在37或25℃下用2 mM氨甲酰苯甲酰胺预孵育，用10 Gy的X射线照射，然后在37或25℃下让细胞修复DNA断裂15、60和120分钟。通过中性彗星试验估计剩余的双链断裂。
在37℃时，在xrs6细胞或中国仓鼠卵巢（野生型）细胞中均未观察到氨甲酰苯甲酰胺处理对修复动力学有影响。相比之下，氨甲酰苯甲酰胺降低了LY-S细胞系中双链断裂的修复，但对LY-R细胞系没有影响，这与之前观察到的多聚（ADP-核糖基化）抑制对LY细胞的放射增敏作用一致。然而，当在25℃下进行照射后孵育时，具有修复能力的细胞系中国仓鼠卵巢细胞和LY-R细胞中的双链断裂重新连接也受到氨甲酰苯甲酰胺的影响。结合早期关于LY-S细胞的数据对这些结果进行分析，已根据拉德福德的辐射损伤固定模型进行了解释。
报道的结果表明，多聚（ADP-核糖基化）可能是DNA损伤转化为致死事件的重要调节因子。
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