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对常规和超高剂量率 (FLASH) 辐射的线粒体反应

Emily G Caggiano, Alan Lopez Hernandez, Trey Waldrop

bioRxiv : the preprint server for biology

|April 28, 2025

概括

超高剂量率 (FLASH) 辐射疗法通过维护线粒体完整性来节省正常细胞,与传统辐射疗法不同. 这一关键机制可以解释FLASH治疗中正常组织毒性的减少,改善患者的治疗结果.

科学领域:

在瘤学瘤学.
辐射生物学辐射生物学
细胞生物学细胞生物学

背景情况:

传统的放射治疗 (CONV) 可以控制瘤,但会导致正常组织的毒性.
超高剂量速率 (FLASH) 辐射疗法 (RT) 在降低毒性并保持有效性方面显示出有前途.
闪光效应的潜在机制在很大程度上是未知的.

研究的目的:

为了研究线粒体完整性在FLASH效应中的作用.
测试FLASH RT在非瘤细胞中保持线粒体功能,降低毒性这一假设.
为了比较FLASH和CONV RT对线粒体健康和瘤结局的影响.

主要方法:

使用体外,体外和体内模型评估线粒体健康和功能.
使用了代谢流量,膜潜力,ROS,DNA损伤,拷贝数和形态学的测试.
在FLASH和CONV RT的反应中评估了瘤生长和生存率.

主要成果:

与CONV RT不同的是,FLASH RT可以使非瘤原生的胰腺细胞免受线粒体损伤.
在小鼠胰腺癌细胞中,FLASH和CONV RT的线粒体损伤类似.
在体内研究表明,在接受FLASH RT治疗的小鼠中,反应率更高,生存时间更长.

结论:

与CONV RT相比,FLASH RT在非瘤源细胞中选择性地保留了线粒体功能.
这种对线粒体完整性的选择性保护是减少正常组织毒性的潜在关键机制.
FLASH RT提供了一种有前途的方法,通过尽量减少副作用来改善癌症治疗结果.

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