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

**Authors:** Abrar Ul Haq Khan, Melinda Blimkie, Bryan Marr, Jin Wu, Tyler Pack, Shelby Kaczmarek, Dong-Hyeon Jo, Holly Laakso, Seung-Hwan Lee

PMC · DOI: 10.3389/fimmu.2025.1635779 · Frontiers in Immunology · 2025-11-03

## TL;DR

This study explores how low-dose gamma radiation affects the immune system and tumor development in mice, finding temporary immune cell changes but minimal impact on cancer progression.

## Contribution

The study provides new evidence on the stimulatory effects of low-dose gamma radiation on natural killer (NK) cells in a mouse model of mammary tumorigenesis.

## Key findings

- Low-dose gamma radiation increased NK cell frequency and IFN-γ production in mice.
- NKG2D expression on NK cells was upregulated following low-dose radiation exposure.
- Despite immune changes, low-dose radiation had minimal impact on mammary tumor development and progression.

## Abstract

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 60Co 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-γ 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.

## Linked entities

- **Proteins:** IFNG (interferon gamma), KLRK1 (killer cell lectin like receptor K1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Klrk1 (killer cell lectin-like receptor subfamily K, member 1) [NCBI Gene 27007] {aka D6H12S2489E, NKG2-D, Nkg2d}
- **Diseases:** tumorigenesis (MESH:D063646), cancer (MESH:D009369), inflammatory (MESH:D007249)
- **Chemicals:** 60Co gamma (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12620402/full.md

## References

100 references — full list in the complete paper: https://tomesphere.com/paper/PMC12620402/full.md

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Source: https://tomesphere.com/paper/PMC12620402