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还原型谷胱甘肽对不同线性能量传递的 X 射线或重离子束诱导的染色体损伤,以及对辐射和博来霉素诱导的 DNA 损伤相互作用的影响。

The influence of reduced glutathione on chromosome damage induced by X-rays or heavy ion beams of different LETs and on the interaction of DNA lesions induced by radiations and bleomycin.

机构信息

Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Mawlai, Meghalaya, India.

出版信息

Mutat Res. 2010 Feb;696(2):154-9. doi: 10.1016/j.mrgentox.2010.01.006. Epub 2010 Jan 25.

Abstract

It is thought that high linear energy transfer (LET) radiation induces more complex DNA damage than low-LET particles, specifically clustered DNA damage that causes cells to repair DNA double strand breaks (DSB) more slowly and leads to severe biological consequences. The present study aimed to investigate the role of exogenously added glutathione (GSH) on (12)C-beam (287keV/mum) and (7)Li-beam (60keV/mum) induced chromosome aberration (CA) formation, particularly on exchange aberration formation. In order to characterize the role of GSH in the joining of DNA DSBs, we induced DNA lesions with bleomycin (Blem) in conjunction with either high- or low-LET radiation (X-rays) since the chemistry of the free DNA ends created by Blem and X-rays is similar. CHO cells were exposed to reduced GSH at a concentration of 2mM for 3h before radiation. Treatment with Blem (20mug/ml) was carried out for 2h before the cells were exposed to radiation. Our results show that the frequency of chromosomal aberration increases with increased LET. Heavy ion exposed cells show a higher frequency of CA over time than do X-irradiated cells. An analysis of the first post-irradiation mitosis of exposed CHO cells shows that high-LET radiation induces more breaks than exchange-type aberrations and exogenous GSH has no influence on high-LET radiation-induced DNA damage. The DNA lesions induced by low-LET radiation interact relatively strongly with Blem-induced lesions whereas interaction between Blem and high-LET radiations was poor. This could be attributed to differences in repair kinetics and qualitative differences in the DNA lesions induced by Blem and high-LET radiation.

摘要

据认为,高线性能量转移(LET)辐射比低 LET 粒子诱导更复杂的 DNA 损伤,特别是簇状 DNA 损伤,导致细胞更缓慢地修复 DNA 双链断裂(DSB),并导致严重的生物学后果。本研究旨在探讨外源性添加谷胱甘肽(GSH)对(12)C 束(287keV/mum)和(7)Li 束(60keV/mum)诱导染色体畸变(CA)形成的作用,特别是交换畸变形成的作用。为了表征 GSH 在 DNA DSB 连接中的作用,我们用博来霉素(Blem)诱导 DNA 损伤,同时用高 LET 或低 LET 辐射(X 射线),因为 Blem 和 X 射线产生的游离 DNA 末端的化学性质相似。CHO 细胞在辐射前用 2mM 的浓度还原 GSH 处理 3 小时。在用 Blem(20ug/ml)处理 2 小时后,再将细胞暴露于辐射下。我们的结果表明,染色体畸变的频率随着 LET 的增加而增加。重离子照射的细胞随着时间的推移显示出更高的 CA 频率,比 X 射线照射的细胞更高。对暴露的 CHO 细胞第一次有丝分裂后分析表明,高 LET 辐射诱导的断裂比交换型畸变更多,外源性 GSH 对高 LET 辐射诱导的 DNA 损伤没有影响。低 LET 辐射诱导的 DNA 损伤与 Blem 诱导的损伤相互作用相对较强,而 Blem 和高 LET 辐射之间的相互作用很差。这可能归因于修复动力学的差异和 Blem 和高 LET 辐射诱导的 DNA 损伤的定性差异。

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