The central theme of our Center is the continued improvement of existing approaches for predicting risk and for ameliorating the side effects of radiation. Our risk and intervention estimators will be based on physical dose, host cytokine balance, and genotoxicity. We will emphasize understanding and mitigating radiationrelated inflammation. In the Center, we direct attention to different aspects of radiation terrorism, but emphasize damage to solid organs at exposures that are not immediately lethal (e.g. low dose chronic exposures, inhalational exposure). We expect that, at the end of the funded period, we will refine physical and biodosimetric markers for victims and, importantly, mitigating agents. Our projects'hypotheses are supported by substantial preliminary data, giving us a high expectation of success in the challenging search for countermeasures. The Center wil also grow through training and mentoring activities. Projects 1 and 2 deal with exposure types (inhalation vs. external low/high LET) and mitigation agents in solid organs, with emphasis on lung, bowel, and cutaneous soft tissues. We have preliminary data on several mitigating agents, including long-term data in mice and positive clinical trials in cancer patients. Project 3 features a technology that uses the spin traps in the carbonate of tooth enamel (or bone) and in sulfate of hair and nails, much in the same way as film dosimetry uses silver nitrate. The trapped spins in dental carbonate are permanent and are measured by in vivo non-invasive electron spin resonance. Projects 4 and 5 feature dosimetry and genotoxicity to the whole body (using an immediate readout on reticulocyte micronuclei) and cutaneous tissues (using keratinocyte micronucei and DNA strand break complex detection). A marrow bioreactor that can powerfully test agents and marrow cell subpopulations will also be used with low and high LET. Project 6 investigates a new cancer therapy that produces localized damage, offering the opportunity for quantitative analysis of lung radiosensitivity and thus a means to test mitigating agents in a human model. Biostatistics Core will assist with experimental design/data analysis in all projects and provide advanced analysis to identify significant markers and make treatment recommendations that integrate the host susceptibility measurements (Projects 1, 2) with physical dose (Project 3) and genotoxicity (Projects 4, 5).
| Zhang, Steven B; Yang, Shanmin; Zhang, Zhenhuan et al. (2017) Thoracic gamma irradiation-induced obesity in C57BL/6 female mice. Int J Radiat Biol 93:1334-1342 |
| Groves, Angela M; Johnston, Carl J; Misra, Ravi S et al. (2015) Whole-Lung Irradiation Results in Pulmonary Macrophage Alterations that are Subpopulation and Strain Specific. Radiat Res 184:639-49 |
| Zhang, Steven B; Yang, Shanmin; Vidyasagar, Sadasivan et al. (2015) PicoGreen assay of circular DNA for radiation biodosimetry. Radiat Res 183:188-95 |
| Yang, Shanmin; Zhang, Mei; Chen, Chun et al. (2015) Triptolide Mitigates Radiation-Induced Pulmonary Fibrosis. Radiat Res 184:509-17 |
| Yin, Liangjie; Vijaygopal, Pooja; Menon, Rejeesh et al. (2014) An amino acid mixture mitigates radiation-induced gastrointestinal toxicity. Health Phys 106:734-44 |
| Chen, Chun; Yang, Shanmin; Zhang, Mei et al. (2013) In vitro Sirius Red collagen assay measures the pattern shift from soluble to deposited collagen. Adv Exp Med Biol 765:47-53 |
| Cherry, Jonathan D; Williams, Jacqueline P; O'Banion, M Kerry et al. (2013) Thermal injury lowers the threshold for radiation-induced neuroinflammation and cognitive dysfunction. Radiat Res 180:398-406 |
| Ma, Jun; Hou, Yanqian; Han, Deping et al. (2013) Fibroblast growth factor-peptide promotes bone marrow recovery after irradiation. Adv Exp Med Biol 765:155-161 |
| Zhang, Mei; Zhang, Bingrong; Guo, Yansong et al. (2013) Alteration of circulating mitochondrial DNA concentration after irradiation. Adv Exp Med Biol 765:371-377 |
| Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal et al. (2013) Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin. Int J Radiat Biol 89:618-27 |
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