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高LET辐射诱导的持续DNA损伤反应信号和胃肠道癌症的发展
Kamendra Kumar1, Santosh Kumar1, Kamal Datta1,2
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Current oncology (Toronto, Ont.)
|June 27, 2023
概括
高能量的太空辐射会导致广泛的DNA损伤,触发诸如衰老之类的细胞反应. 这可以通过持续的DNA损伤反应促进炎症和瘤信号传递导致胃肠道癌症.
科学领域:
- 天体生物学 天体生物学
- 辐射生物学 辐射生物学
- 在瘤学瘤学.
背景情况:
- 电离辐射 (IR) 剂量,剂量速率和线性能量转移 (LET) 决定了DNA损伤.
- 与低LET辐射相比,太空中的高LET重离子会导致广泛的DNA损伤.
- 细胞对DNA损伤的反应包括通过DNA损伤反应 (DDR) 信号的恢复,细胞死亡,衰老或增殖.
研究的目的:
- 审查DNA损伤,DDR,细胞衰老和SASP在胃肠道 (GI) 癌症发生中的相互作用.
- 探索慢性太空辐射暴露如何增加肠胃表皮中的瘤发生风险.
主要方法:
- 对电离辐射,DNA损伤反应和细胞衰老研究的文献综述.
- 对参与胃肠道癌症发展的信号通路的分析. 辐射暴露后.
主要成果:
- 持续的DNA损伤和DDR改变可以导致体质基因突变.
- 红外诱导的衰老细胞可以获得与衰老相关的分泌表型 (SASP).
- SASP信号可以驱动瘤性途径并加速胃肠道癌症的进展.
结论:
- DNA损伤,DDR,衰老和SASP驱动的炎症的复杂相互作用在肠道癌症发生中至关重要.
- 长期暴露于太空辐射对胃肠道瘤发生的风险很大.
- 了解这些机制对于开发对抗辐射诱导癌症的对策至关重要.
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