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Radiation Accidents: Preclinical Model Study We propose that a comprehensive, integrated research program be established between the Johns Hopkins University (JHU) and the Armed Forces Radiobiological Research Institute (AFRRI) in the areas in order to define human biological response to non-homogeneous patterns of ionizing radiation. Rationale: These types of radiation exposure can be anticipated in victims of radi- ,‘(I 2- 0 I ) Flash exposure -- neutrons or gamma 2) A continuous gradually decreasing low dose rate exposure. 3 ) Flash exposure, followed by a more protracted exposure at lower 4 ) Flash exposure, recovery period, followed by #2. 5) Flash exposure, radioprotection, followed by #2.
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Optimal management of victims will depend on early dosimetry, application of the right radiobiological information, and the selection of the most appropriate treatment for that given situation. Emerging new information from separate projects in AFRRI (Mac Vittie et al.) and JHOC (Williams et al.) indicates that fresh approaches to the areas of dosimetry, radiobiology and treatment can be made in a vastly improved experimental animal model. Prospects for obtaining new information that would be of great benefit to radiation accident victims are excellent. Moreover the emerging principles would be of great benefit to the application of radiolabeled immunoglobulins in the treatment of human cancer patients. Recent studies indicate that current models do not well predict_--1. the response of humans to non-homogeneous dose patterns, especially high-low dose rate patterns. The gastrointestinal syndrome may be especially sensitive to
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3. Under certain conditions high/low dose-rates are much more cytotoxic than is predicted using data from constant-dose-rate experi4. Current dosimetric techniques estimate levels in exposed human beings only after considerable delay, making triage less precise and therapy less effective. 5 . Alternate possible treatment modalities for radiation injury can have considerable morbidity and mortality; therefore, more exact criteria for their application must be defined. comparison to human patient response Vader (Variable Dose Rate Irradiator) goyttrium, 1 1 IIndium, 131Iodine labeled antiferritin
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Proposed Dosimetric Studies 1. Chromosomal studies, lymphocytes and bone marrow 2. Hair apoptosis (skin dose) 5 . Hematopoietic cell response Proposed Radiobiological Studies -- high dose followed by low dose -- augmentation of current studies but at higher rates 2. Acute sensitization to more protracted radiation patterns
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2. Kinetics of stem cell response in vivo bone marrow transplantation Animal models. Both rats and dogs have been developed for in-depth analysis of radiation biology problems both at JHU and AFRRI. The rat has an advantage in size and cost, as well as in developing new models for control of radiation damage to the small intestine. The dog will show the same inhomogeneous dose distribution as experienced by human radiation accident victims. Dog bone marrow has the same low concentration of hemopoietic stem cells as human bone marrow.