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快中子辐照下人淋巴细胞 DNA 双链断裂的形成和修复与剂量率的关系。

The Impact of Dose Rate on DNA Double-Strand Break Formation and Repair in Human Lymphocytes Exposed to Fast Neutron Irradiation.

机构信息

Department of Radiochemistry, South African Nuclear Energy Corporation, Pretoria 001, South Africa.

Radiobiology, Radiation Biophysics Division, Department of Nuclear Medicine, iThemba LABS, Cape Town 7131, South Africa.

出版信息

Int J Mol Sci. 2019 Oct 28;20(21):5350. doi: 10.3390/ijms20215350.

Abstract

The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) (66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (LDR) and 1.29 ± 0.45 (HDR) at 24 h postirradiation, remaining significantly higher than background levels. This illustrates a significant effect of dose rate on neutron-induced DNA damage. While no significant difference was observed in residual DNA damage after 24 h, the DSB repair half-life of LDR exposure was slower than that of HDR exposure. The results give a first indication that the dose rate should be taken into account for cancer risk estimations related to neutrons.

摘要

由于缺乏关于生物系统如何应对低剂量和低剂量率暴露的信息,因此难以准确评估致癌风险。这对于空间辐射至关重要,空间辐射仍然是长期载人太空探索的一个严重问题。在这项研究中,使用 γ-H2AX 焦点分析来跟踪暴露于中子辐照后 DNA 双链断裂 (DSB) 的诱导和修复,中子辐照是空间环境中产生的次级辐射。人类淋巴细胞暴露于高剂量率 (HDR:0.400 Gy/min) 和低剂量率 (LDR:0.015 Gy/min) ((66)/Be(40)) 中子。在暴露于中子剂量范围为 0.125 至 2 Gy 后 30 分钟,研究了 DNA DSB 的诱导。在 1 Gy 中子剂量后不同时间点研究了修复动力学。我们的结果表明,与 LDR 暴露相比,HDR 暴露时 γ-H2AX 焦点形成高 40%。最大 γ-H2AX 焦点水平在照射后 24 小时逐渐降低至 1.65±0.64 焦点/细胞 (LDR) 和 1.29±0.45 (HDR),仍明显高于背景水平。这说明剂量率对中子诱导的 DNA 损伤有显著影响。尽管在 24 小时后未观察到残留 DNA 损伤的显著差异,但 LDR 暴露的 DSB 修复半衰期比 HDR 暴露慢。结果首次表明,在与中子相关的癌症风险估计中应考虑剂量率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2e8/6862539/d28cd81f08c2/ijms-20-05350-g001.jpg

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