Hematopoietic growth factors (HGF) are recommended therapy for high dose radiation exposure but unfavorable administration schedules requiring early and repeat dosing limit the logistical ease with which they can be used. humanPEG-G-CSF murinePEG-GM-CSF or humanPEG-IL-11. Mice were administered one of the HGF analogs at 24-28hr post irradiation and in some studies additional doses given every other day (beginning with the 24-28hr dose) for a total of 3 or 9 doses. 30d survival was significantly increased with only one dose of 0.3mg kg?1 PD184352 (CI-1040) of PEG-G-CSF and PEG-IL-11 or three doses of 0.3mg kg?1 of PEG-GM-CSF (p≤0.006). Enhanced survival correlated with consistently and significantly enhanced WBC NE RBC and PLT recovery for PEG-G- and PEG-GM-CSF and enhanced RBC and PLT recovery for PEG-IL-11 (p≤0.05). Longer administration schedules or higher doses did not provide a significant additional survival benefit over the shorter lower dose schedules. These data demonstrate the efficacy of BBT’s PEG-HGF to provide significantly increased survival with fewer injections and lower drug doses which may have significant economic and logistical value in the aftermath of a radiation event. PD184352 (CI-1040) INTRODUCTION The increasing presence worldwide of radioactive material for therapeutic energy or weapon applications underscores the need for medical preparedness for effective treatment in the event of accidental PD184352 (CI-1040) or intentional radiation exposure. However there are currently no medical countermeasures (MCM) approved to treat severely irradiated individuals and physicians would likely rely on medications used in chemo- and radiotherapy-induced myelosuppression such as hematopoietic cytokines in addition to supportive care. Supportive care such as antibiotics and fluids can significantly increase the lethal radiation dose for 50% of humans at 60 days post-exposure (LD50/60) from 3.5-4.5 Gy to ~6-7 Gy (Lushbaugh 1969 Vriesendorp and Van Bekkum 1984 Dainiak 2002 Anno et al. 2003). As such supportive care will be an important factor in treating irradiated individuals. Doses in the range of 2-10 Gy affect primarily the rapidly dividing bone marrow hematopoietic cells resulting in the hematopoietic (H) syndrome of the acute irradiation syndrome (H-ARS). H-ARS is characterized by a decrease in all classes of white blood cells (WBC) erythrocytes and platelets resulting in life-threatening neutropenia and thrombocytopenia and possible death due to infection and/or bleeding. Stimulation of the hematopoietic system with hematopoietic CPB2 growth factors (HGF) to enhance production of neutrophils and platelets remains one of the key mitigation strategies for H-ARS. Hematopoietic growth factors such as granulocyte-colony stimulating factor (G-CSF) are commonly used to accelerate recovery from chemotherapy-induced neutropenia. G-CSF has been shown to improve survival of animals exposed to otherwise lethal radiation when administered shortly after exposure (Schuening et al. 1989). MacVittie et al. (MacVittie et al. 2005) reported that 17% of dogs exposed to 4 Gy and treated with vehicle survived 30 days PD184352 (CI-1040) whereas 100% of dogs receiving daily subcutaneous (sc) injections of 0.01mg kg?1 G-CSF for 23 days survived for 30 days. Studies in the authors’ lab (Plett et al. 2012) have shown that daily administration of 0.125mg kg?1 G-CSF beginning 24h post-irradiation and continuing until day time 16 resulted in 65% survival of treated mice vs 30% survival in settings. Improved survival correlated with accelerated neutrophil (NE) recovery in G-CSF-treated animals (Plett et al. 2012). Solitary administration of G-CSF or murine GM-CSF did not provide a survival benefit when given to lethally-irradiated mice (Neta 1988 Neta et al. 1988) unless given within 2 hours of radiation (Sureda et al. 1993). Hematopoietic growth factors used to treat hematopoietic complications of chemotherapy such as G-CSF GM-CSF and IL-11 are typically given by daily subcutaneous (sc) injections for 16-23 days limiting the appeal of these factors for the treatment of H-ARS inside a mass casualty radiation event. In the aftermath of such an emergency patient figures will become high and medical facilities inundated making daily.