Long term objectives are to evaluate Bis 3,5-diisopropylsaliclatocopper (II) Cu(II)(3,5-dips)2 treatment regimens for radioprotection of cells grown in culture and mice irradiated with clinically relevant doses of X- and gamma-radiation (40-170 rads/minute to deliver 800 to 1000 rads), and evaluate effects of radiation and treatment (0, 60, 80, or 100 mg/kg) on essential metalloelement metabolism and immunocompetency of mice.
Specific aims of this proposal are to synthesize sufficient quantities of Cu(II) (3,5-dips)2 to enable studies of its radioprotectant activity. Radioprotectant activity will be determined by measuring survival of irradiated cultured cells and whole-body irradiated mice. Survival and treatment regimen will be correlated for irradiated cells grown in culture. Altered essential metalloelement metabolism and immunocompetency will be determined for irradiated and treated mice. Survival, alteration of plasma, liver, spleen, intestine, brain, and bone marrow copper content as well as immunocompetency will be correlated for irradiated and treated mice. Routine synthetic procedures will be used to synthesize Cu(II)(3,5-dips)2. Atomic absorption spectrophotometric methods will be used to determine tissue copper content. Colony formation, as measured with Puck-Marcus single cell techniques, will be used to determine irradiated-cell survival. Survival will also be used to measure the in vivo radioprotectant activity. Immunocompetency will be determined by evaluating the abilities of different lymphocyte subclasses to repopulate hosts with determinations of spleen cell markers, mitogen responsiveness, and bone marrow colony forming units. Antibody responsiveness will be measured using the Jerne plaque-forming assay and determinations of cell-mediated immunity will be measured using oxazolone hypersensitivity and mixed lymphocyte reactivity. Appropriate statistical programs will be used to evaluate significance of differences found in these studies.
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