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Induction of Cell Death through Alteration of Oxidants and Antioxidants in Lung Epithelial Cells Exposed to High Energy Protons

机译:通过改变氧化剂和诱导细胞死亡 高能质子暴露于肺上皮细胞中的抗氧化剂

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摘要

Radiation affects several cellular and molecular processes, including double strand breakage and modifications of sugar moieties and bases. In outer space, protons are the primary radiation source that poses a range of potential health risks to astronauts. On the other hand, the use of proton irradiation for tumor radiation therapy is increasing, as it largely spares healthy tissues while killing tumor tissues. Although radiation-related research has been conducted extensively, the molecular toxicology and cellular mechanisms affected by proton irradiation remain poorly understood. Therefore, in this study, we irradiated rat lung epithelial cells with different doses of protons and investigated their effects on cell proliferation and death. Our data show an inhibition of cell proliferation in proton-irradiated cells with a significant dose-dependent activation and repression of reactive oxygen species and antioxidants glutathione and superoxide dismutase, respectively, compared with control cells. In addition, the activities of apoptosis-related genes such as caspase-3 and -8 were induced in a dose-dependent manner with corresponding increased levels of DNA fragmentation in proton-irradiated cells compared with control cells. Together, our results show that proton irradiation alters oxidant and antioxidant levels in cells to activate the apoptotic pathway for cell death.
机译:辐射会影响几种细胞和分子过程,包括双链断裂和糖部分和碱基的修饰。在外层空间,质子是主要的辐射源,对宇航员构成一系列潜在的健康风险。另一方面,质子辐射在肿瘤放射治疗中的使用正在增加,因为它在杀死肿瘤组织的同时极大地节省了健康组织。尽管已广泛进行了与辐射有关的研究,但对质子辐射影响的分子毒理学和细胞机制仍知之甚少。因此,在这项研究中,我们用不同剂量的质子辐照了大鼠肺上皮细胞,并研究了它们对细胞增殖和死亡的影响。我们的数据显示,与对照细胞相比,质子辐照细胞的细胞增殖抑制具有显着的剂量依赖性激活和抑制活性氧以及抗氧化剂谷胱甘肽和超氧化物歧化酶。此外,与质子辐照的细胞相比,质子辐照细胞中凋亡相关基因的活性(例如caspase-3和-8)以剂量依赖性方式被诱导,DNA片段的水平相应增加。总之,我们的结果表明质子辐照会改变氧化剂和 细胞中的抗氧化剂水平激活细胞的凋亡途径 死亡。

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