Abstract
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 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.
Highlights
The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome
In this report we identified an optimal dose of administration for the compound (0.3 mg/kg) and demonstrated an accelerated recovery in bone marrow colony forming units, peripheral blood cell counts, sternal cellularity, megakaryocyte numbers, and circulating levels of serum biomarkers
For the delayed effects of acute radiation exposure (DEARE) (Table 1) studies, animals from the two highest doses of radiation (9.5 and 10.0 Gy) that were administered formulation buffer (FB) were grouped into a single group, referred to as the FB group; in addition, three distinct groups of animals administered BBT-059 24 h prior to TBI (n = 10 for each www.nature.com/scientificreports group) were kept including those irradiated at 10.5 Gy, 11.5 Gy, and 12 Gy for long term studies (6 months and 12 months collection points), these groups will be referred to as 10.5 Gy BBT-059, 11.5 Gy BBT-059, and 12.0 Gy BBT-059, respectively
Summary
The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. 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 this report we identified an optimal dose of administration for the compound (0.3 mg/kg) and demonstrated an accelerated recovery in bone marrow colony forming units, peripheral blood cell counts, sternal cellularity, megakaryocyte numbers, and circulating levels of serum biomarkers. These studies monitored the status of the animals and indicated parameters for 30 days following TBI
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