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快中子的剂量反应和相对生物效应:诱导成年小鼠海马区细胞凋亡和抑制神经发生。

Dose-response and relative biological effectiveness of fast neutrons: induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice.

机构信息

Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, Buk-Gu, Gwangju, South Korea.

出版信息

Int J Radiat Biol. 2010 Jun;86(6):476-85. doi: 10.3109/09553001003667990.

DOI:10.3109/09553001003667990
PMID:20470197
Abstract

PURPOSE

Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET (60)Co gamma-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG).

MATERIALS AND METHODS

The mice were exposed to 35 MeV fast neutrons or (60)Co gamma-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation.

RESULTS

The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or gamma-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4-8) and DCX (8-32) were approximately 3.2 and 2.5 times, respectively, the effects of gamma-rays at the same dose.

CONCLUSIONS

Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and gamma-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.

摘要

目的

本研究比较了高线性能量转移(LET)快中子与低 LET(60)Coγ射线对成年 ICR 小鼠海马中细胞凋亡诱导和神经发生减少的影响,以评估快中子在成年海马齿状回(DG)中的相对生物学效应(RBE)。

材料和方法

将小鼠暴露于 35 MeV 快中子或(60)Coγ射线中。我们在单次全身照射后立即评估了海马中细胞凋亡的发生率以及 Ki-67(一种最初由单克隆抗体 Kiel-67 定义的细胞增殖蛋白标志物)和双皮质素(DCX:一种未成熟祖细胞标志物)的表达。

结果

DG 中末端脱氧核苷酸转移酶(TdT)介导的 dUTP 缺口末端标记(TUNEL)阳性凋亡核的数量增加,Ki-67 和 DCX 阳性细胞的数量均呈剂量依赖性下降,无论是快中子还是γ射线。在海马中,DG 中的凋亡频率在 2 到 8 之间,快中子的 RBE 约为 1.9。此外,快中子对 Ki-67(4-8)和 DCX(8-32)表达频率的抑制作用分别约为γ射线相同剂量的 3.2 倍和 2.5 倍。

结论

在暴露于快中子和γ射线后,海马 DG 中凋亡细胞死亡增加和神经发生减少呈剂量依赖性。此外,不同辐射质量对海马神经发生的不同影响率可能是 RBE 的一个指标。

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