The purpose and the long-term objective of this proposed research is to understand the mechanism involved in the expression of variable sensitivity to total body radiation in rats. A vast number of studies on the biological effects of ionizing radiation in experimental animals suggest, amongst many other effects, a disturbance in the hemopoietic system leading to a life span shortening. However, rats of Filcher strain have been found in our laboratory to be more resistant to whole-body gamma radiation compared to rats of two other strains. There is a genetic difference in rat hemoglobin Beta- chain structure, with alternate alleles, A and B at a single locus. The proposed research intends to study whether genetic factors closely linked to the rat-beta-globin gene structure influence the radioresistivity in the Filcher strain. The plan of study includes: I. Chromatographic separation of rat hemoglobin components from normal AA and BB adults and irradiated AA and BB adults and to establish the proportional variation during radiation. II. Comparison of resistivity between inbred Filcher and a few other inbred and Outbred strains of rats in regard to drug-mediated, bleeding- induced and radiation-related challenges. III. Quantitation of erythroid progenitors in response to total-body radiation in rats of Filcher and other strains of same age. IV. Assessment of some radioprotective factors in the sera of irradiated rats and comparison with the sera of irradiated Filcher rats using clonal culture, radioimmunoassay and chromatographic procedures. All these concerted studies should lead to increased knowledge of mechanism which regulates radioresistivity in rats of Filcher strain. As for humans, our rat study may lead to a better understanding of radiation-induced variable effects in nuclear accident victims and in patients undergoing radiation therapy. Another important objective of this proposal is to provide an opportunity to undergraduate and graduate students, particularly in the departments of chemistry and biology, of Tuskegee University to receive adequate research training, in an effort to motivate them to pursue a career in biomedically oriented fields.
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