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Mitigating Radiation-induced Bone Loss via Dietary Modulation of Inflammatory Cytokines

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Mitigating Radiation-induced Bone Loss via Dietary Modulation of Inflammatory Cytokines
Proposal Summary: Astronauts traveling to Mars or other planetary surfaces will be exposed to low doses (up to 2 Gy) of high-energy radiation particles that compose galactic cosmic radiation (GCR). A growing body of literature documents a rapid acceleration of bone resorption activity and some suppression of bone-forming cells after exposure to even very low doses of space-relevant radiation. One of the key mechanisms proposed for these changes is an increase in pro-inflammatory cytokines like TNF-a. We already know that International Space Station (ISS) crew members consuming a diet rich in omega-3 Fatty acids (FAs) experience smaller reductions in bone mineral density over 6-month missions than do fellow astronauts consuming a diet low in these FAs. This project proposes to investigate the impact of consuming a diet high in omega-3 FAs on radiation-induced pro-inflammatory cytokines. Hence, this simple dietary intervention may provide a low-cost, low-risk means of countering the harmful effects of radiation on bone integrity.

A currently funded NASA Space Biology study based at Texas A&M (Principal Investigator (PI): Dr. Nancy Turner) will expose multiple cohorts of mice at Brookhaven National Laboratory’s NASA Space Radiation Laboratory (NSRL) facility to space relevant doses of high energy iron particles) over the next 12 months. Her project will determine the selective impact of radiation on radio-sensitive intestinal stem cells in two sets of animals: those consuming a corn oil-supplemented diet simulating the average American diet and those consuming a diet supplemented with fish oil, which elevates dramatically omega-3 FA intake. The PI’s current collaborations with Dr. Turner and our laboratories’ close proximity have enabled an unparalleled tissue sharing opportunity.

We propose to collect both long bones and serum from these animals to test our over-arching hypothesis: a diet high in omega-3 FAs will mitigate radiation-induced bone loss by reducing the generation of inflammatory cytokines in bone tissue. The study offers the possibility of comparing responses to 3 different space-relevant doses (0.1, 0.25, and 0.5 Gy) of 56Fe at 1 Gev/nucleon, along with a gamma reference group (0.25 to 2 Gy). Analyses of specimens collected at 12 hours post-exposure will focus on changes in pro-inflammatory cytokines in serum and in bone cells called osteocytes, which in turn signal to both bone-forming and bone-resorbing cells. The two later post-irradiation time points proposed (4 wk and 8 wk) will enable us to determine early and late effects on bone cell activity and bone structural integrity, important since the current data base on time course of bone alterations post-exposure is sparse.

Significance : Given that the expensive NSRL (NASA Space Radiation Laboratory) live animal experiments are already funded, this project can yield a wealth of new data important to minimizing fracture risk for exploration class missions at minimal extra cost to NASA. With this project we will generate a comprehensive assessment of the impact of 3 doses of high-energy iron particles on bone integrity, at 3 dose levels and at 3 time points post-irradiation. Comparisons with gamma-irradiated groups at comparable doses will allow for RBE (relative biological effectiveness) determinations; sham irradiated animals will be sacrificed at the same time points. After just one year, we will have proof-of-concept and feasibility testing completed for a high omega-3 FA diet as a countermeasure to radiation-induced bone loss, and interesting science data on the role of osteocytes in the pro-inflammatory response to radiation. Should it prove successful, this countermeasure is ready for immediate operational implementation, as omega-3 fatty acid-rich diets and/or supplements are available now to ISS crew. These data will also be relevant to clinical patients undergoing radiotherapy and patients with chronic inflammatory disease (e.g., inflammatory bowel disease), all of whom experience significantly elevated fracture rates.

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