Metabolomic Studies of Tissue Injury in Nonhuman Primates Exposed to Gamma-Radiation.

Amrita K Cheema,Stephen Y Wise,Oluseyi O Fatanmi,Vijay K Singh,Meena U Rajagopal,Khyati Y Mehta

doi:10.3390/ijms20133360

Abstract

Exposure to ionizing radiation induces a complex cascade of systemic and tissue-specific responses that lead to functional impairment over time in the surviving population. However, due to the lack of predictive biomarkers of tissue injury, current methods for the management of survivors of radiation exposure episodes involve monitoring of individuals over time for the development of adverse clinical symptoms and death. Herein, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that were exposed to a single dose of 7.2 Gy whole-body 60Co γ-radiation that either survived or succumbed to radiation toxicities over a 60-day period. This study involved the delineation of the radiation effects in the liver, kidney, jejunum, heart, lung, and spleen. We found robust metabolic changes in the kidney and liver and modest changes in other tissue types at the 60-day time point in a cohort of NHPs. Remarkably, we found significant elevation of long-chain acylcarnitines in animals that were exposed to radiation across multiple tissue types underscoring the role of this class of metabolites as a generic indicator of radiation-induced normal tissue injury. These studies underscore the utility of a metabolomics approach for delineating anticipatory biomarkers of exposure to ionizing radiation.

Highlights

Nuclear accidents, such as Chernobyl and Fukushima–Daiichi, and deliberate radiological events by terrorists have been at the forefront of emergency response planning [1,2,3]
Untargeted Metabolomics Analysis Identifies Changes in the Tissue Metabolome of the nonhuman primates (NHPs) Exposed to Radiation
Accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of an improvised nuclear device (IND) or a radiological dispersal device (RDD) in a metropolitan city have led to an increased need for the rapid assessment of exposure to different radiation qualities and dose

Summary

Introduction

Nuclear accidents, such as Chernobyl and Fukushima–Daiichi, and deliberate radiological events by terrorists have been at the forefront of emergency response planning [1,2,3]. The threat of terrorism or military action has escalated the possible use of radiological or nuclear weapons. The atomic bombings of Hiroshima and Nagasaki have demonstrated the power of nuclear weapons to cause harm to humans through morbidity, mortality, and long-term effects arising from radiation exposure. The detonation of an improvised nuclear device (IND) or a radiological dispersal device (RDD) requires an immediate assessment of exposed victims for the absorbed radiation dose. While an RDD will expose individuals to relatively low levels of radiation, an IND can lead to significant exposure and death to thousands of people [4]. Protection of citizens from national health security threats continues to be a high priority for the government

Methods

Results

Conclusion