Blood-Based Biomarkers for the Preterminal Stage Using Rhesus Macaques Exposed to Acute Total-Body Radiation
Acute radiation syndrome is characterized by progressive hematologic decline and biochemical imbalances, yet the transition from recoverable injury to the preterminal state remains incompletely characterized using routine laboratory assays. Prior proteomic, metabolomic, and transcriptomic studies have revealed biological signatures in preterminal serum and plasma samples from irradiated nonhuman primates, suggesting that the preterminal state represents a distinct phenotype. In this study, complete blood count and serum biochemistry data collected from male and female rhesus macaques (Macaca mulatta) exposed to total-body doses of 60Co γ-radiation were monitored from seven days prior to irradiation through 60 days post-irradiation. Preterminal samples were collected immediately prior to euthanasia upon determination of moribundity. A series of analyses was performed to characterize differences in injury severity and recovery between survivors and non-survivors. Our findings showed shared early cytopenic decreases in both survivors and non-survivors, consistent with expected radiation-induced hematopoietic injury. Preterminal samples collected between days 14–22 post-irradiation were characterized by erythroid decline and lymphocyte depletion. Most notably, red blood cells, hemoglobin, and hematocrit showed a delayed decline, with significant decreases associated with non-survival. Serum chemistry data was less discriminatory during scheduled sampling, but preterminal comparisons demonstrated significant changes prior to mortality. These results suggest that conventional clinical metrics can help characterize the preterminal phenotype.