Radiation Metabolomics: Current Status and Future Directions

Abstract

Human exposure to ionizing radiation (IR) disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as organ- and tissue-specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high-resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic IR. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure.

Effects of ionizing radiation on the heart

“…Common circulating markers of cardiac injury from various causes, such as troponins, atrial natriuretic peptide, and brain natriuretic peptide have been tested as early identifiers of cardiac radiation injury in patients, with varying results [125–131]. Studies are increasingly focused on finding molecular markers that can specifically indicate radiation injury [132], and new sensitive high-throughput technologies prove to be useful [133]. The goal of these studies is to identify biomarkers that can distinguish cardiovascular radiation toxicity from cardiovascular disease due to other causes.…”

Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules

“…Multiple reviews have detailed the technological aspects of radiation biodosimetry (Patterson et al, 2010, Coy et al, 2011, Di Girolamo et al, 2013, Menon et al, 2016), while others have focused on the strengths and challenges of this newer –omics field (Johnson and Gonzalez, 2012, Patti et al., 2012). Briefly, nuclear magnetic resonance ( 1 H-NMR or NMR) had been the platform of choice historically, with samples analyzed in a non-destructive manner and because it provided information on the structure of a given biomarker (Menon et al, 2016).…”

“…Briefly, nuclear magnetic resonance ( 1 H-NMR or NMR) had been the platform of choice historically, with samples analyzed in a non-destructive manner and because it provided information on the structure of a given biomarker (Menon et al, 2016). However, the tendency of NMR to identify high abundance molecules due to low sensitivity, left many metabolites undiscovered that could serve as biomarkers of a given injury.…”

Assessment of Saliva as a Potential Biofluid for Biodosimetry: A Pilot Metabolomics Study in Mice

“…To date, we have explored the value of such markers in rodents, nonhuman primates, and total-body-irradiated humans with very encouraging results and significant cross-species validation (4–8). In this pilot study, we extended our studies to assess the utility of saliva as a biofluid for biodosimetry through metabolomics at day 1 and 7 postirradiation, time points that have been previously investigated with other biofluids (1, 4, 6, 7, 9–11). Since the salivary glands as well as oral mucosa are highly radiosensitive, this can be translated in products of radiation exposure directly present in saliva from cells undergoing cell death (12, 13).…”