Delayed effects of acute whole body lethal radiation exposure in mice pre-treated with BBT-059

• Published in: Scientific reports 2020-04, Vol.10 (1), p.6825, Article 6825
• Main Authors: Sharma, Neel K., Holmes-Hampton, Gregory P., Kumar, Vidya P., Biswas, Shukla, Wuddie, Kefale, Stone, Sasha, Aschenake, Zemenu, Wilkins, William L., Fam, Christine M., Cox, George N., Ghosh, Sanchita P.
• Format: Article
• Language: English
• Subjects: 13/51; 14/19; 631/136/7; 64/60; 692/53/2423; Alkaline Phosphatase - blood; Animals; Aspartate Aminotransferases - blood; Blood Cell Count; Bone marrow; Cadherins - metabolism; Clone Cells; Colony-Forming Units Assay; Dose-Response Relationship, Radiation; Drug dosages; E-cadherin; Gamma Rays; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - radiation effects; Humanities and Social Sciences; Interleukin-11 - pharmacology; Irradiation; Kidney - pathology; Kidney - radiation effects; Kidneys; Liver - pathology; Liver - radiation effects; Long term; Lysates; Male; Medical prognosis; Mice; multidisciplinary; Organ Specificity - radiation effects; Peripheral blood; Radiation Exposure; Science; Science (multidisciplinary); Senescence; Spleen; Survival Analysis; Whole-Body Irradiation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-63818-7

The 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 60 Co 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.