Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model

Abstract

Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

Biological effects of space radiation and development of effective countermeasures

“…The changes in peripheral leukocytes have also been examined in ferrets irradiated with 60 Co or 137 Cs γ-rays and 110-MeV protons (141, 142) and Yucatan minipigs irradiated with 6-MeV electrons (130), 6+12-MeV electrons and SPE protons (143, 144). …”

“…In the Yucatan minipigs irradiated with SPE-like protons with energies of 155 MeV or below, the WBC count decreased significantly within a day post- irradiation with a single skin dose of up to 10 Gy (143). Between day-1 and day-4 post- irradiation, the WBC count reached the lowest level, and then recovered slowly thereafter.…”

“…Based on the WBC, lymphocyte and neutrophil count data for the minipigs exposed to 6+12 MeV electron radiation (144) and simulated SPE radiation (143), RBE values were calculated for the effect of simulated SPE radiation on leukocytes in irradiated animals. The results show that the RBE value for the simulated SPE radiation varied with both the radiation dose and the time post-irradiation (144).…”

Increased intracranial pressure in mini-pigs exposed to simulated solar particle event radiation

“…The rationale for the large animal model is a multi-systems approach for studying the biological effects of SPE radiation. Other parameters, including simulated SPE radiation-induced skin and hematopoietic cell changes are reported elsewhere [15, 31]. It is reasonable that changes in ICP be studied in a large animal model system (like the porcine model) versus a small animal model (rodent) system, because the phylogeny of humans is closer to pigs than that of rodents.…”

“…Our current experiments utilize the Yucatan mini-pig model system exposed to simulated proton or electron SPE radiation to investigate multi-systemic changes induced by SPE radiation, including radiation effects on the skin and hematopoietic systems [14–16]. The prescribed skin doses used in these experiments range from 2.5–20 Gy (estimated range of doses received during an SPE, in the spacecraft, as well as during extravehicular activity [6]).…”