Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

Abstract

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.

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 6-MeV electrons at a total skin dose of 25 Gy, the WBC count decreased significantly on day-1 post-irradiation, and then recovered by day-7 and increased significantly above the pre-irradiation level by day-30 after irradiation (130). The WBC count did not change significantly in any other dose groups irradiated with electrons at a dose of 15 Gy or below.…”

“…The dosimetry involved in determining simulated SPE radiation doses in pigs is illustrated in Figure 1, which shows that the doses to the external organs (e.g., skin, eyes) are very high, while the doses to internal organs (e.g., spinal cord, bone marrow) are quite low. The detailed methods for determining the organ doses are described elsewhere (130, 131). These methods incorporate modern radiation oncology approaches of computed tomography (CT) based Monte Carlo dosimetry into the studies so that acute biological effects in specific organ systems can be determined in animal model systems, and radiation toxicity from various types of SPE radiation exposures can be compared.…”

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.…”

“…For the electron radiation exposure, the setup has been previously described [14, 15]. Briefly, a Clinac iX linear accelerator (LINAC) (Varian Medical Systems, Palo Alto, CA) was used to deliver 6 MeV and 12 MeV electrons in alternating intervals at a source to skin distance of 5 m, delivered to one side of the long axis of the animal’s body.…”