The Human Salivary Proteome is Radiation Responsive

Abstract

In the event of a nuclear incident in a heavily populated area, the surge in demand for medical evaluation will likely overwhelm our emergency care system, compromising our ability to care for victims with life-threatening injuries or exposures. Therefore, there exists a need for a rapidly deployable biological assay for radiation exposure that can be performed in the field by individuals with little to no medical training. Saliva is an attractive biofluid for this purpose, due to the relative ease of its collection and the wide array of biomolecules it contains. To determine whether the human salivary proteome is responsive to ionizing radiation exposure, we characterized the abundances of salivary proteins in humans before and after total body irradiation. Using an assay panel targeting 90 analytes (growth factors, chemokines and cytokines), we identified proteins that were significantly radiation responsive in human saliva. The responses of three proteins (monocyte chemo-attractant protein 1, interleukin 8 and intercellular adhesion molecule 1) were confirmed using independent immunoassay platforms and then verified and further characterized in 130 saliva samples from a completely independent set of 38 patients undergoing total body irradiation. The results demonstrate the potential for detecting radiation exposure based on analysis of human saliva.

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

“…Salivary glands and the oral mucosa are highly radiosensitive tissues (Moore et al, 2014), resulting in severe reduction to saliva production within the first week post-exposure that can lead to mucositis, dysphagia, and nutrient malabsorption (Grundmann et al, 2009, Pernot et al, 2014). Differences in electrolytes and enzymes such as amylase have already been reported to be directly associated with radiation exposure (Pernot et al, 2014, Soni et al, 2016), and salivary biomarkers have provided discriminatory power in various cancers and disease states (Tsuruoka et al, 2013, Mikkonen et al, 2014, Zhang et al, 2014b).…”

State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure

“…Using 2D-DIGE analysis in this study, similar trends were also observed in the serum proteome profiles of locally irradiated mice and one human patient who accidently received an acute partial-body radiation exposure ( 38 ). In one recent study of human saliva, the salivary proteome of single- and accumulated-fraction TBI patients was screened, and IL8, MCP-1 and ICAM-1 were identified as radiation-responsive proteins with elevated expression after exposure, which correlated with accumulated dose; and in another study evaluating cytokine levels in saliva from patients undergoing head and neck radiotherapy, a dose-response relationship was reported for expression of IL4, IL6, IL8, EGF, VEGF, MCP-1 and TNF-a ( 39 , 40 ). The utility of proteomic markers of radiation response in a variety of models has been demonstrated, and the evaluation of FL, citrulline, oxysterols and other protein markers has even been incorporated into the medical management of recent radiological incidents ( 41 , 42 ).…”

Oral Biofluid Biomarker Research: Current Status and Emerging Frontiers

“…As other studies have further shown, the salivary proteome can be used to draw connections between saliva and cystic fibrosis, diabetes, periodontitis, dental caries, and acquired immune deficiency syndrome (AIDS) [28,29,30,31,32]. Salivary proteomic analysis may even be useful for health safety applications such as radiation exposure [33,34,35]. A particularly compelling application of salivary proteomic biomarkers is the application to oral squamous cell carcinoma (OSCC).…”