在纤维细胞中G2/M检查点停止受损后,炎症性基因表达恶化,来自表现出严重不良反应的患者
Takahiro Oike1,2, Ken Okuda3, Shunji Haruna3
1Department of Radiation Oncology, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.
Advances in radiation oncology
|July 12, 2024
概括
遗传因素可能导致放射治疗 (RT) 期间的严重炎症. 辐射敏感纤维细胞 (RS-Fs) 中G2/M检查点停止受损导致DNA损伤和炎症基因表达增加,这表明RT不良影响的潜在预测标志物.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 辐射疗法 (RT) 已先进向瘤,但遗传因素可能导致患者严重的副作用.
- 研究辐射诱导炎症背后的机制对于改善患者的治疗结果至关重要.
研究的目的:
- 调查放射治疗 (RT) 期间炎症恶化的机制.
- 确定潜在的基因标记物,用于预测对RT的不良炎症反应.
主要方法:
- 从一个患有严重RT副作用的患者 (辐射敏感纤维细胞,RS-Fs) 的皮肤纤维细胞与正常纤维细胞进行了比较.
- 评估了离子辐射 (IR) 后的微核形成,G2/M检查点停止,DNA损伤修复和炎症基因表达.
主要成果:
- 在IR之后,RS-F显示微核形成增加和G2/M检查点过早释放,这表明有未修复的DNA双链断裂 (DSB) 的线粒分裂.
- 在IR后的RS-F中观察到受损的DSB末端切除和ATR-Chk1通路激活.
- RS-Fs表现出高度上调的炎症基因表达,与微核形成和先天免疫反应有关.
结论:
- 由于缺陷的DSB末端切除和ATR-Chk1通路激活,G2/M检查点停止受损,导致RT期间炎症恶化.
- 参与G2/M检查点停止的基因可以作为放射治疗意外炎症反应的预测标记.
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