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自由基清除剂预处理的乳腺癌和肺癌细胞中 γ 射线诱导的 DNA 损伤的生物学后果。

Biological outcomes of γ-radiation induced DNA damages in breast and lung cancer cells pretreated with free radical scavengers.

机构信息

a Vinča Institute of Nuclear Sciences , University of Belgrade , Belgrade , Serbia.

b CNRS-IN2P3 CENBG Université Bordeaux , Gradignan , France.

出版信息

Int J Radiat Biol. 2019 Mar;95(3):274-285. doi: 10.1080/09553002.2019.1549753. Epub 2019 Jan 22.

DOI:10.1080/09553002.2019.1549753
PMID:30451568
Abstract

PURPOSE

Investigation of effects on DNA of γ-irradiated human cancer cells pretreated with free radical scavengers is aimed to create reference data which would enable assessment of the relative efficiency of high linear energy transfer (LET) radiations used in hadron therapy, i.e. protons and carbon ions.

MATERIALS AND METHODS

MCF-7 breast and HTB177 lung cancer cells are irradiated with γ-rays. To minimize indirect effects of irradiation, dimethyl sulfoxide (DMSO) or glycerol are applied as free radical scavengers. Biological response to irradiation is evaluated through clonogenic cell survival, immunocytochemical and cell cycle analysis, as well as expression of proteins involved in DNA damage response.

RESULTS

Examined cell lines reveal similar level of radioresistance. Application of scavengers leads to the rise of cell survival and decreases the number of DNA double strand breaks in irradiated cells. Differences in cell cycle and protein expression between the two cell lines are probably caused by different DNA damage repair mechanisms that are activated.

CONCLUSION

The obtained results show that DMSO and glycerol have good scavenging capacity, and may be used to minimize DNA damage induced by free radicals. Therefore, they will be used as the reference for comparison with high LET irradiations, as well as good experimental data suitable for validation of numerical simulations.

摘要

目的

研究经自由基清除剂预处理的γ 射线辐照人癌细胞对 DNA 的影响,旨在为评估用于强相互作用治疗(即质子和碳离子)的高传能线密度(LET)射线的相对效率创建参考数据。

材料与方法

用γ 射线辐照 MCF-7 乳腺癌和 HTB177 肺癌细胞。为了最小化辐照的间接效应,应用二甲基亚砜(DMSO)或甘油作为自由基清除剂。通过集落形成细胞存活、免疫细胞化学和细胞周期分析以及参与 DNA 损伤反应的蛋白质表达来评估对辐照的生物学反应。

结果

所研究的细胞系显示出相似的放射抗性水平。清除剂的应用导致细胞存活增加,并减少辐照细胞中双链 DNA 断裂的数量。两种细胞系之间的细胞周期和蛋白表达的差异可能是由激活的不同 DNA 损伤修复机制引起的。

结论

获得的结果表明,DMSO 和甘油具有良好的清除能力,可用于最小化自由基诱导的 DNA 损伤。因此,它们将被用作与高 LET 辐照进行比较的参考,以及适合数值模拟验证的良好实验数据。

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