The Impact of Dose, Sex, and Age at Time of Acute Whole-body Radiation Exposure on Long-term Hematopoiesis in Rhesus Macaques (Macaca mulatta).

Abstract

The hematopoietic system is highly sensitive to ionizing radiation exposure. Accumulating evidence from the Japanese A-bomb survivor cohort and animal studies suggests that radiation-induced damage to the hematopoietic system can persist long after exposure, and therefore has the potential of contributing to delayed effects of acute radiation exposure (DEARE). In this study, archival data from the non-human primate radiation late effects cohort was analyzed to evaluate long-term effects on the hemopoietic system. The dataset included white blood cell and leukocyte differential counts from two hundred sixteen rhesus macaques (Macaca mulatta) exposed to 1.14 to 8.5 Gy and 47 non-irradiated control animals; blood samples were collected approximately 1-year post-acute uniform whole-body exposure and continuously thereafter every 2-6 months. Linear mixed models were developed for total leukocyte and differential counts, which included neutrophil, lymphocyte, and monocyte counts and percentages. Longitudinal trends were estimated for three dose ranges (low dose LD50/30, 6.8 to 8.5 Gy) and controls, and adjusted for sex and age at time of exposure. All models suggested that radiation dose was a statistically significant factor in the longitudinal trends of leukocyte and differential changes observed. Control and low-dose irradiated non-human primates (NHPs) presented a slight decrease in total leukocyte count and monocyte skewed differentiation, consistent with changes expected from natural aging of the hematopoietic system; longitudinal changes for the mid-dose LD50/30 NHPs than for the controls and