|| Overall hypothesis: Low-dose radiation induces molecular manifestations of a pro-inflammatory response as a function of radiation type, radiation doses, doses rates, LET (linear energy transfer) value, and time. An oral available anti-inflammatory countermeasure, already in human clinical trials with a good safety profile, will significantly reduce proton and HZE-ion (high charge energy-ion) exposure associated tumor initiation and progression.
The overarching hypothesis for this project is that space radiation induces molecular manifestations of a pro-inflammatory response as a function of radiation type, radiation doses, doses rates, LET value, and time. We are testing if an oral available anti-oxidant and anti-inflammatory countermeasure, already in human clinical trials with a good safety profile, CDDO, significantly reduces proton and HZE-ion exposure associated tumor initiation and progression. Based on experiments conducted at the NASA Space Radiation Laboratory (Brookhaven, NY) we demonstrate that HZE ion components of GCR (galactic cosmic radiation) result in persistent DNA damage and inflammatory signaling, increased mutations in tumor suppressor genes, and higher rates of cancer initiation and progression compared to that seen with similar doses of terrestrial radiation. While physical shielding may reduce some of the risks of space radiation, there is substantial evidence that biological countermeasures will be required to ensure that the established safety limits of increased lifetime fatal cancer risks are not exceeded. We are conducting GCR simulations consisting of fast switching between protons, helium, and silicon using a dose rate of 0.5 cGy/min and a total combined dose of between 27-30 cGy to more closely mimic the space environment on a trip to Mars and back. Finally, we are conducting experiments with the official NASA GCRsim with acute and protracted mixed fields.
Kim, S.B., Bozeman, R.G., Kaisani, A., Kim, W., Zhang, L., Richardson, J.A., Wright, W.E., and Shay, J.W. Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses. Oncogene. 2015. https://doi.org/10.1038/onc.2015.395
Norbury, J.W., Schimmerling, W., Slaba, T.C., Edouard Azzam, Francis F. Badavi, Giorgio Baiocco, Eric Benton, Veronica Bindi, Eleanor A. Blakely, Steve R. Blattnig, David A. Boothman, Thomas B. Borak, Richard A. Britten, Stan Curtis, Michael Dingfelder, Marco Durante, William Dynan, Amelia Eisch, S. Robin Elgart, Dudley T. Goodhead, Peter M. Guida, Lawrence H. Heilbronn, Christine E. Hellweg, Janice L. Huff, Amy Kronenberg, Chiara La Tessa, Derek Lowenstein, Jack Miller, Taksahi Morita, Livio Narici, Gregory A. Nelson, Ryan B. Norman, Takeo Ohnishi, Andrea Ottolenghi, Zarana S. Patel, Guenther Reitz, Adam Rusek, Ann-Sofie Schreurs, Lisa A. Scott-Carnell, Edward Semones, Jerry W. Shay, Vyacheslav A. Shurshakov, Lembit Sihver, Lisa C. Simonsen, Michael Story, Mitchell S. Turker, Yukio Uchihori, Jacqueline Williams, Cary J. Zeitlin. Galactic cosmic ray simulation at the NASA Space Radiation Laboratory. Life Sciences in Space Research 8:38-51, 2016. PMID: 26948012
Lutiel, K. Bozeman, R., Kaisani, A. Kim, S.B., Barron, S., Richardson, J.A., Shay, J.W. Proton radiation-induced cancer progression. Life Sciences in Space Research, 2018. https://doi.org/10.1016/j.lssr.2018.08.002
Luitel, K., Kim, S.B., Barron, S. Richardson, J.A. and Shay, J.W. Lung cancer progression using fast switching multiple ion beam irradiation and countermeasure prevention, Life Sciences in Space Research, 2019. DOI: 10.1016/j.lssr.2019.07.011