Multicentered Biospecimen Analyses after 4 Gy Sublethal Total Body Irradiation in Rhesus Macaques.

Abstract

In the event of a large-scale radiological emergency, delivering timely medical aid to individuals receiving potentially lethal doses of radiation will result in improved survival and decreased severity of injuries. While it may be possible to reconstruct a dose estimate based on a location during the event and/or early symptoms presenting after the event, limitations with readily available information and inaccuracy of that estimate may not provide enough certainty for successful medical triage. Thus, individual biodosimetry assessments would assist medical professionals in providing prompt care to those who would benefit the most. In this study, a variety of accessible biospecimens (blood, plasma, serum, feces, saliva, and urine) from eight rhesus macaques irradiated with a single total body sublethal dose of 4 Gy of 60Co γ rays were collected before and up to 60 days after exposure for distribution to 10 different investigators' work sites for site-specific analyses. Results showing statistically significant changes in hematology parameters as well as gene, protein, and metabolite expression have since been published. Here, these results are combined and integrated with new data from microRNA (miRNA) expression in plasma samples as well as 16S rRNA sequencing and metabolomics data from fecal samples. A total of 40 unique miRNAs were significantly expressed on days 3, 6, 30, or 60. Metabolomic analysis of fecal samples found changes in multiple pathways, including steroid hormones, C18 (sex) hormones, and bile acid synthesis. Temporal changes were found in the gut microbiome for microbial abundance and richness. Finally, a retrospective view of the collective results demonstrated common overlapping pathways that were enriched from significantly altered biomarkers. This large, collaborative study from a single irradiated cohort demonstrates the utility of multiple timepoints, biospecimen types, and omics technologies that collectively identified 61 common biomarkers across 4 omics platforms that were enriched for pathways relevant to an acute radiation injury to the hematopoietic system that may aid future radiation biodosimetry efforts.