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慢性束缚应激与低剂量 56Fe 粒子辐照协同作用对 Trp53 杂合小鼠染色体畸变的诱导。

Synergistic Effects of Chronic Restraint-Induced Stress and Low-Dose 56Fe-particle Irradiation on Induction of Chromosomal Aberrations in Trp53-Heterozygous Mice.

机构信息

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba.

Center for Advanced Radiation Emergency Medicine, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.

出版信息

Radiat Res. 2021 Jul 1;196(1):100-112. doi: 10.1667/RADE-20-00218.1.

DOI:10.1667/RADE-20-00218.1
PMID:33901294
Abstract

Astronauts can develop psychological stress (PS) during space flights due to the enclosed environment, microgravity, altered light-dark cycles, and risks of equipment failure or fatal mishaps. At the same time, they are exposed to cosmic rays including high atomic number and energy (HZE) particles such as iron-56 (Fe) ions. Psychological stress or radiation exposure can cause detrimental effects in humans. An earlier published pioneering study showed that chronic restraint-induced psychological stress (CRIPS) could attenuate Trp53 functions and increase carcinogenesis induced by low-linear energy transfer (LET) γ rays in Trp53-heterozygous (Trp53+/-) mice. To elucidate possible modification effects from CRIPS on high-LET HZE particle-induced health consequences, Trp53+/- mice were received both CRIPS and accelerated Fe ion irradiation. Six-week-old Trp53+/- C57BL/6N male mice were restrained 6 h per day for 28 consecutive days. On day 8, they received total-body Fe-particle irradiation (Fe-TBI, 0.1 or 2 Gy). Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Induction of psychological stress in our experimental model was confirmed by increase in urinary corticosterone level on day 7 of restraint regimen. Regardless of Fe-TBI, CRIPS reduced splenocyte number per spleen at the end of the 28-day restraint regimen. At 2 Gy, Fe-TBI alone induced many aberrant chromosomes and no modifying effect was detected from CRIPS on induction of aberrant chromosomes. Notably, neither Fe-TBI at 0.1 Gy nor CRIPS alone induced any increase in the frequency of aberrant chromosomes, while simultaneous exposure resulted in a significant increase in the frequency of chromosomal exchanges. These findings clearly showed that CRIPS could enhance the frequency of chromosomal exchanges induced by Fe-TBI at a low dose of 0.1 Gy.

摘要

宇航员在太空飞行中会由于封闭的环境、微重力、改变的光暗周期以及设备故障或致命事故的风险而产生心理压力(PS)。与此同时,他们还会暴露在宇宙射线中,包括高原子数和能量(HZE)粒子,如铁-56(Fe)离子。心理压力或辐射暴露会对人类造成有害影响。之前发表的一项开创性研究表明,慢性束缚诱导的心理压力(CRIPS)可以减弱 Trp53 功能,并增加低线性能量转移(LET)γ射线在 Trp53 杂合(Trp53+/-)小鼠中诱发的癌变。为了阐明 CRIPS 对高 LET HZE 粒子引起的健康后果的可能修饰作用,Trp53+/- 小鼠同时接受 CRIPS 和加速 Fe 离子照射。六周龄的 Trp53+/- C57BL/6N 雄性小鼠每天束缚 6 小时,连续 28 天。在第 8 天,它们接受全身 Fe 粒子照射(Fe-TBI,0.1 或 2 Gy)。在 28 天束缚方案结束时,从脾细胞制备中期染色体展开物,并使用染色体 1(绿色)、2(红色)和 3(黄色)的荧光原位杂交(FISH)探针进行染色。在束缚方案第 7 天,通过尿液皮质酮水平的增加证实了我们实验模型中心理压力的诱导。无论是否进行 Fe-TBI,CRIPS 都会在 28 天束缚方案结束时减少脾细胞数量。在 2 Gy 时,Fe-TBI 单独照射会诱导许多异常染色体,而 CRIPS 对诱导异常染色体没有修饰作用。值得注意的是,0.1 Gy 的 Fe-TBI 或单独的 CRIPS 均不会增加异常染色体的频率,而同时暴露则会导致染色体交换频率显著增加。这些发现清楚地表明,CRIPS 可以增强 0.1 Gy 低剂量 Fe-TBI 诱导的染色体交换频率。

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