Ionizing radiation affects miRNA composition in both young and old mice

Abstract

Purpose: Humans are exposed to both natural (e.g. soil, cosmic rays) and human-made radiation sources (e.g. medical devices, nuclear energy production) on a daily basis. The use of medical radiation sources such as Computed Tomography (CT) scans and X-ray has increased rapidly, especially in the treatment of older populations. Micro Ribonucleic Acids (miRNAs) are the major regulators of multiple low-dose radiation-induced biological processes through post-translational inhibition. As a result, understanding age-related changes of miRNA profiles that may compromise the population after low dose radiation exposure has become increasingly important.

Materials and methods: In this study, we irradiated both young (2 months) and old (26 months) C57BL/6J mice with low dose radiation (10 mGy and 100 mGy at 1 mGy/min using an open beam ⁶⁰Co gamma source) and checked the miRNA expression profiles.

Results: The global miRNA expression of old mice was significantly reduced compared to that of young mice. Low dose radiation at 10 mGy significantly increased the global miRNA expression in both old and young mice one week following irradiation, which suggests that 10 mGy low dose radiation may reverse the global inhibition effects of aging on miRNA expression. Higher 100 mGy radiation slightly reduced the global expression of miRNAs. We also identified several miRNAs that were elevated or reduced in all of the radiation treatment groups; these can be further explored as candidates for the radiation-induced bio-markers.

Conclusions: The results of our study demonstrate that both radiation and aging can influence the global expression of miRNAs, while low dose radiation modulates the expression of miRNAs in a dose-, time-, and age-dependent manner.

Keywords:

• Radiation
• low dose radiation
• miRNA
• biomarker
• biodosimetry

Acknowledgements

The authors would like to thank Yevgeniya Le, Sheila Kramer-Tremblay, and Joanne Ball (CNL) for carefully reviewing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Michelle Bugden

Michelle Bugden is the Veterinary Technologist, Research Technologist with the Radiobiology section at Canadian Nuclear Laboratories. Provides technical support with animal health research and biological effects of low dose radiation, with primary focus on cancer research.

Sukhmani Billing

Sukhmani Billing is a CO-OP student and performed the experiments.

Kei Cheng Mak

Kei Cheng Mak is a CO-OP student and performed the experiments.

Farrah Norton

Farrah Norton is a Research Scientist and Lead of the Biodosimetry emergency response and research capability at Canadian Nuclear Laboratories (CNL) in Chalk River, Ontario. She graduated from the University of Guelph in Ontario, with a BSc in Biological Sciences and from The Michener Institute of Applied Health Sciences in Toronto, Ontario with a DipHSc (Genetics). Her work at CNL involves being a partner in the Federal Nuclear Emergency Plan (FNEP) as part of the human monitoring group for emergency response in biodosimetry as well as her research, which involves development of dose estimation methods for large scale exposures to ionizing radiation for high throughput.

Dmitry Klokov

Dmitry Klokov, PhD in Radiobiology, currently he is a head of Radiobiology section at Canadian Nuclear Laboratories and an Adjunct Professor at the Department of Biochemistry, Microbiology and Immunology of University of Ottawa. His research interests lie broadly in various areas of Radiobiology, with a focus on low doses.

Yi Wang

Dr. Yi Wang is a research scientist at Radiobiology and Health Branch, Canadian Nuclear Laboratories, and an adjunct professor at Department of Biochemistry, Microbiology and Immunology, University of Ottawa. His research focus has been in the area of understanding the effects of low dose radiation on heath and disease development, and using low dose radiation to treat cancer. He is also interested in finding the next-generation radiation induced biomarkers.