Abstract
AbstractThe threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we describe the use of a promising radiation countermeasure, BBT-059, and the results of a long term mouse study (up to 12 months) in the male CD2F1 strain using 60Co gamma irradiation (~0.6 Gy/min, 7.5–12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation.
Funder
United States Department of Defense | Uniformed Services University | Armed Forces Radiobiology Research Institute, Uniformed Services University
AFRRI Intramural funding RAB23338
Publisher
Springer Science and Business Media LLC
Reference59 articles.
1. Administration, U.S. FDA, http://1.usa.gov/22Aj474 (Silver Spring, MD, 2015).
2. Administration, U.S. FDA, http://1.usa.gov/1Tpsbov (Silver Spring, MD: U.S, 2015).
3. Administration, U.S. FDA. FDA approves Leukine for Acute Radiation Syndrome. (2018).
4. Health, U. D. o., Services, H., Food & Administration, D. (2017).
5. Paul, S. R. et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proceedings of the National Academy of Sciences of the United States of America 87, 7512–7516, https://doi.org/10.1073/pnas.87.19.7512 (1990).
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