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Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice
The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306076/ https://www.ncbi.nlm.nih.gov/pubmed/34298925 http://dx.doi.org/10.3390/ijms22147303 |
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author | Khan, Abrar Ul Haq Blimkie, Melinda Yang, Doo Seok Serran, Mandy Pack, Tyler Wu, Jin Kang, Ji-Young Laakso, Holly Lee, Seung-Hwan Le, Yevgeniya |
author_facet | Khan, Abrar Ul Haq Blimkie, Melinda Yang, Doo Seok Serran, Mandy Pack, Tyler Wu, Jin Kang, Ji-Young Laakso, Holly Lee, Seung-Hwan Le, Yevgeniya |
author_sort | Khan, Abrar Ul Haq |
collection | PubMed |
description | The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands. |
format | Online Article Text |
id | pubmed-8306076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83060762021-07-25 Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice Khan, Abrar Ul Haq Blimkie, Melinda Yang, Doo Seok Serran, Mandy Pack, Tyler Wu, Jin Kang, Ji-Young Laakso, Holly Lee, Seung-Hwan Le, Yevgeniya Int J Mol Sci Article The Linear-No-Threshold (LNT) model predicts a dose-dependent linear increase in cancer risk. This has been supported by biological and epidemiological studies at high-dose exposures. However, at low-doses (LDR ≤ 0.1 Gy), the effects are more elusive and demonstrate a deviation from linearity. In this study, the effects of LDR on the development and progression of mammary cancer in FVB/N-Tg(MMTVneu)202Mul/J mice were investigated. Animals were chronically exposed to total doses of 10, 100, and 2000 mGy via tritiated drinking water, and were assessed at 3.5, 6, and 8 months of age. Results indicated an increased proportion of NK cells in various organs of LDR exposed mice. LDR significantly influenced NK and T cell function and activation, despite diminishing cell proliferation. Notably, the expression of NKG2D receptor on NK cells was dramatically reduced at 3.5 months but was upregulated at later time-points, while the expression of NKG2D ligand followed the opposite trend, with an increase at 3.5 months and a decrease thereafter. No noticeable impact was observed on mammary cancer development, as measured by tumor load. Our results demonstrated that LDR significantly influenced the proportion, proliferation, activation, and function of immune cells. Importantly, to the best of our knowledge, this is the first report demonstrating that LDR modulates the cross-talk between the NKG2D receptor and its ligands. MDPI 2021-07-07 /pmc/articles/PMC8306076/ /pubmed/34298925 http://dx.doi.org/10.3390/ijms22147303 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khan, Abrar Ul Haq Blimkie, Melinda Yang, Doo Seok Serran, Mandy Pack, Tyler Wu, Jin Kang, Ji-Young Laakso, Holly Lee, Seung-Hwan Le, Yevgeniya Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title | Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title_full | Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title_fullStr | Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title_full_unstemmed | Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title_short | Effects of Chronic Low-Dose Internal Radiation on Immune-Stimulatory Responses in Mice |
title_sort | effects of chronic low-dose internal radiation on immune-stimulatory responses in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306076/ https://www.ncbi.nlm.nih.gov/pubmed/34298925 http://dx.doi.org/10.3390/ijms22147303 |
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