<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators"^^ . "Purpose: To evaluate the effectiveness of mitigation of acute ionizing radiation damage by mitochondrion-targeted small molecules. Methods and Materials: We evaluated the ability of nitroxide-linked alkene peptide isostere JP4-039, the nitric oxide synthase inhibitor-linked alkene peptide esostere MCF201-89, and the p53/mdm2/mdm4 protein complex inhibitor BEB55 to mitigate radiation effects by clonogenic survival curves with the murine hematopoietic progenitor cell line 32D cl 3 and the human bone marrow stromal (KM101) and pulmonary epithelial (IB3) cell lines. The p53-dependent mechanism of action was tested with p53+/+ and p53-/- murine bone marrow stromal cell lines. C57BL/6 NHsd female mice were injected i.p. with JP4-039, MCF201-89, or BEB55 individually or in combination, after receiving 9.5 Gy total body irradiation (TBI). Results: Each drug, JP4-039, MCF201-89, or BEB55, individually or as a mixture of all three compounds increased the survival of 32D cl 3 (p = 0.0021, p = 0.0011, p = 0.0038, and p = 0.0073, respectively) and IB3 cells (p = 0.0193, p = 0.0452, p = 0.0017, and p = 0.0019, respectively) significantly relative to that of control irradiated cells. KM101 cells were protected by individual drugs (p = 0.0007, p = 0.0235, p = 0.0044, respectively). JP4-039 and MCF201-89 increased irradiation survival of both p53+/+ (p = 0.0396 and p = 0.0071, respectively) and p53 -/- cells (p = 0.0007 and p = 0.0188, respectively), while BEB55 was ineffective with p53-/- cells. Drugs administered individually or as a mixtures of all three after TBI significantly increased mouse survival (p = 0.0234, 0.0009, 0.0052, and 0.0167, respectively). Conclusion: Mitochondrial targeting of small molecule radiation mitigators decreases irradiation-induced cell death in vitro and prolongs survival of lethally irradiated mice. © 2011 Elsevier Inc."^^ . "2011-07-01" . . "80" . "3" . . "International Journal of Radiation Oncology Biology Physics"^^ . . . "03603016" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "B"^^ . "Beck"^^ . "B Beck"^^ . . "T"^^ . "Dixon"^^ . "T Dixon"^^ . . "W"^^ . "Wang"^^ . "W Wang"^^ . . "MC"^^ . "Frantz"^^ . "MC Frantz"^^ . . "JS"^^ . "Greenberger"^^ . "JS Greenberger"^^ . . "H"^^ . "Wang"^^ . "H Wang"^^ . . "JP"^^ . "Goff"^^ . "JP Goff"^^ . . "A"^^ . "Doemling"^^ . "A Doemling"^^ . . "P"^^ . "Wipf"^^ . "P Wipf"^^ . . "D"^^ . "Shields"^^ . "D Shields"^^ . . "Y"^^ . "Tyurina"^^ . "Y Tyurina"^^ . . "MW"^^ . "Epperly"^^ . "MW Epperly"^^ . . "VE"^^ . "Kagan"^^ . "VE Kagan"^^ . . "JCM"^^ . "Rwigema"^^ . "JCM Rwigema"^^ . . "D"^^ . "Franicola"^^ . "D Franicola"^^ . . . . . . "Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators (Plain Text)"^^ . . . "licence.txt"^^ . . . "Two strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #18756 \n\nTwo strategies for the development of mitochondrion-targeted small molecule radiation damage mitigators\n\n" . "text/html" . .