Whole mouse blood microRNA as biomarkers for exposure to 𝛄-rays and ⁵⁶Fe ions

Abstract

Purpose: Biomarkers of ionising radiation exposure are useful in a variety of scenarios, such as medical diagnostic imaging, occupational exposures, and spaceflight. This study investigates to what extent microRNA (miRNA) expression signatures in mouse peripheral blood can be used as biomarkers for exposures to radiation with low and high linear energy transfers.

Materials and methods: Mice were irradiated with doses of 0.5, 1.5, or 5.0 Gy γ-rays (dose rate of 0.0136 Gy/s) or with doses of 0.1 or 0.5 Gy ⁵⁶Fe ions (dose rate of 0.00208 Gy/s). Total RNA was isolated from whole blood at 6 h or 24 h after irradiation. Three animals per irradiation condition were used. Differentially expressed miRNA were determined by means of quantitative real-time polymerase chain reaction.

Results: miRNA expression signatures were radiation type-specific and dose- and time-dependent. The differentially expressed miRNA were expressed in either one condition (71%) or multiple conditions (29%). Classifiers based on the differentially expressed miRNA predicted radiation type or dose with accuracies between 75% and 100%. Gene-ontology analyses show that miRNA induced by irradiation are involved in the control of several biological processes, such as mRNA transcription regulation, nucleic-acid metabolism, and development.

Conclusion: miRNA signatures induced by ionising radiation in mouse blood are radiation type- and radiation dose-specific. These findings underline the complexity of the radiation response and the importance of miRNA in it.

Keywords:

• microRNA
• biodosimetry
• whole body irradiation
• high-LET radiation
• class prediction
• gene ontology analysis

Acknowledgements

We are grateful to the staff at the NASA Space Radiation Laboratory and at the Medical and Biology Departments of Brookhaven National Laboratory. In particular, we wish to thank Drs Adam Rusek, Michael Sivertz, and I-Hung Chiang for their help with dosimetry and irradiation of animals, and Dr Peter Guida for his organisational support. Additionally, we acknowledge the assistance of MaryAnn Petry and the staff of the Brookhaven Animal Facility. This study was supported in part by NASA, grant number NNX07AT41G, and by the Center for High-Throughput Minimally-Invasive Radiation Biodosimetry, National Institute of Allergy and Infectious Diseases, grant number U19 AI067773.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.