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低剂量 γ 射线对自发性乳腺肿瘤发生小鼠模型免疫调节的影响

英文原题:The impact of low-dose gamma radiation on immune modulation in a mouse model of spontaneous mammary gland tumorigenesis.

查看英文原题

The impact of low-dose gamma radiation on immune modulation in a mouse model of spontaneous mammary gland tumorigenesis.

PubMed 2025/11/03(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

了解低剂量电离辐射暴露的影响具有重要的公共卫生意义。然而,低剂量电离辐射对免疫调节和癌症进展的影响仍存在争议。本研究旨在使用转基因小鼠模型,探讨慢性低剂量伽马辐射对乳腺肿瘤发生和免疫稳态的影响。雌性MMTV-neu转基因小鼠连续56天接受全身60Co伽马辐射,累积吸收剂量分别为10、100和2,000 mGy。在3.5、6和8月龄时分析小鼠的免疫细胞组成和功能变化,以及肿瘤发展情况。

我们发现,暴露于低剂量辐射的小鼠表现出NK细胞频率的短暂增加,并且在体外刺激后IFN-产生得到改善。值得注意的是,低剂量辐射暴露后,NK细胞上NKG2D的表达上调。低剂量辐射还调节了炎症细胞因子谱和免疫细胞群体,如巨噬细胞和髓源性抑制细胞。尽管存在这些免疫变化,但对肿瘤发生的总体影响很小。虽然我们的数据表明低剂量辐射治疗不影响生存和癌症进展,但观察到的NK细胞比例、活化和功能结果提供了低剂量辐射对NK细胞刺激作用的证据。这些发现旨在为健康风险评估做出贡献,并为辐射防护法规提供建议。

展开英文摘要原文

Understanding the impacts of low-dose ionizing radiation exposure has significant public health implications.

However, the effects of low-dose ionizing radiation on immune modulation and cancer progression remain contentious.

This study aimed to investigate the impact of chronic low-dose gamma radiation on mammary tumorigenesis and immune homeostasis using a transgenic mouse model. Female MMTV-neu transgenic mice were exposed to continuous whole-body 60 Co gamma radiation over a period of 56 days, thereby receiving cumulative absorbed doses of 10, 100 and 2,000 mGy. Mice were analyzed at 3. 5, 6 and 8 months of age for changes in immune cell composition and function, as well as tumor development.

We found that mice exposed to LDR exhibited transient increases in NK cell frequency, along with improved IFN- production following ex vivo stimulation.

Notably, the expression of NKG2D on NK cells was upregulated following LDR exposure. Low-dose radiation also modulated inflammatory cytokine profiles and immune cell populations, such as macrophages and myeloid-derived suppressor cells. Despite these immune changes, the overall impact on tumorigenesis was minimal. Although our data indicated that the LDR treatment did not impact survival and cancer progression, the observed results of NK cell proportion, activation and function provide evidence of the stimulatory effects of LDR on NK cells.

These findings aim to contribute to health risk assessments and advise radiation protection regulations.

论文信息

作者
Khan AUH、Blimkie M、Marr B、Wu J、Pack T、Kaczmarek S、Jo DH、Laakso H
单位
Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.Canada
期刊
Frontiers in immunology2025
原文标识
PubMed 41256861 · DOI 10.3389/fimmu.2025.1635779