Center for Biophysical Assessment and Risk Management

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DESCRIPTION (provided by applicant): 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 radiation-related 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 will 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 micronuclei 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. 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).