Dynamic imaging analysis reveals Auger electron-emitting radio-cisplatin induces DNA damage depending on the cell cycle
Dynamic imaging analysis reveals Auger electron-emitting radio-cisplatin induces DNA damage depending on the cell cycle
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动态成像分析揭示俄歇电子发射放射性顺铂根据细胞周期诱导 DNA 损伤
DOI：
10.1016/j.bbrc.2022.11.016
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发表时间：
2022
影响因子：
3.1
通讯作者：
Zhang Ming-Rong
中科院分区：
文献类型：
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作者：
Obata Honoka;Kurimasa Akihiro;Muraoka Tadanori;Tsuji Atsushi B.;Kondo Katsuya;Kuwahara Yoshikazu;Minegishi Katsuyuki;Nagatsu Kotaro;Ogawa Mikako;Zhang Ming-Rong
俄歇电子能对DNA产生纳米级的物理化学损伤。本研究报告了具有DNA结合能力的俄歇电子发射剂放射性标记的顺铂对双链断裂（DSB）等DNA损伤与细胞周期之间的关系进行了连续和系统的评价。对于动态成像分析，我们使用表达两种荧光融合蛋白的U2 OS衍生的癌细胞：具有绿色荧光蛋白的肿瘤抑制剂p53结合蛋白1（53 BP 1-EGFP）和具有红色荧光蛋白的增殖细胞核抗原（PCNA-DsRed）。使用具有deepImageJ插件和Google Colaboratory平台的ImageJ软件定量分析细胞的延时图像。从中期到晚期G1期，在G1到S期的过渡，我们发现增加53 BP 1灶在细胞与放射性顺铂治疗。在G1期，放射性顺铂比非放射性顺铂和生理盐水引起更多的DSB，但在其他阶段没有。这些结果表明，俄歇电子诱导的DNA损伤，包括DSB，依赖于细胞周期。G1期与低DNA修复能力和高放射敏感性相关，是一个有前途的靶点;因此，将放射性标记的顺铂与将细胞阻滞在G1期的药物结合可以改善俄歇电子的DNA损伤作用及其治疗效果。
Auger electrons can induce nanoscale physiochemical damage to DNA. The present study reports a sequential and systematic evaluation of the relationship between DNA damage such as double-strand breaks (DSBs) and the cell cycle for the Auger electron-emitting agent radiolabeled cisplatin with DNA binding ability. For dynamic imaging analysis, we used U2OS-derived cancer cells expressing two fluorescent fusion proteins: tumor-suppressor p53 binding protein 1 with a green fluorescent protein (53BP1-EGFP) and proliferating cell nuclear antigen with a red fluorescent protein (PCNA-DsRed). Time-lapse images of the cells were quantitatively analyzed using the ImageJ software with the deepImageJ plugin and the Google Colaboratory platform. From the middle-to-late G1 phase, around the G1-to-S phase transition, we found increased 53BP1 foci in cells treated with the radio-cisplatin. The radio-cisplatin caused significantly more DSBs than the nonradioactive cisplatin and saline in the G1 phase but not in the other phases. These results indicate that Auger electron-induced DNA damage, including DSBs, depends on the cell cycle. The G1 phase, which is associated with low DNA repair capacity and high radiosensitivity, is a promising target; thus, combining radiolabeled cisplatin with agents that arrest cells in the G1 phase could improve the DNA-damaging effect of Auger electrons and their therapeutic efficacy.