PNNL

Abstract

Missions beyond low-Earth orbit (LEO) will expose astronauts to radiation in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR), including high-energy and charge (HZE) nuclei. Though GCR HZE flux intensity is relatively low, radiobiological effectiveness can be fairly high. Unfortunately, the limited understanding of the biological effects of this unique radiation environment confound risk assessments for planned missions to the moon and Mars. The gastrointestinal (GI) system is highly sensitive to ionizing radiation (IR) - even relatively low dose IR exposures induce mucosal lesions and disrupt epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC), yet most studies to-date examining the GI effects of SEP/GCR exposure were performed in the tumor-prone APC mouse model of CRC. Studies are thus needed in normal/healthy models to better define the GI risks associated with SEP/GCR exposure and test novel medical countermeasures (MCMs) to ensure astronaut safety. We therefore performed ground-based studies in which we exposed wild-type C57BL/6J mice to: gamma-rays; protons (SEP); 16O ions (GCR); or 56Fe ions (GCR) and used histology and immunohistochemistry to define SEP/GCR-induced GI alterations. Our data show that unlike gamma-rays, exposure to Mars mission-equivalent doses of SEP/GCR disrupts intestinal function during the first 24 hrs post-IR, inducing DNA double-strand breaks (DSBs and apoptosis, and inducing mucosal lesions, vascular congestion, loss of epithelial barrier function, and marked swelling of lymph nodes. Significantly from the standpoint of astronaut safety, we show pre-treatment with a novel MCM consisting of curcumin-laden nanolipoprotein particles (cNLPs) protects the GI system, significantly reducing DSBs and the incidence of apoptosis. These data thus improve our understanding of the physiological alterations that occur in the normal GI tract following exposure to the types and doses of radiation to which astronauts will be exposed during long-duration missions beyond LEO.