The purpose of the proposed application is to investigate the ability of lithium to enhance hematopoietic recovery or prevent hematopoietic damage after cytotoxic drug exposure. By measuring hematologic blood indices, pluripotential (CFU-S) and committed stem cells (CFU-GM,CFU-E/BFU-E), the hematopoietic inductive microenvironment (HIM) by the stroma colony assay (CFU-Str) and quantitating kinetic changes in the turnover of stem cells from marrow and spleen after lithium administration (210 mg/kg b.w.) before or after cytotoxic drug exposure (vinblastine, cyclophosphamide, colchicine, actinomycin and cytosine arabinoside) regimen similar to that used clinically in man, should derive knowledge on the extent of lithium influencing hematopoietic recovery. It is therefore imperative that new methods be developed to reduce the degree and duration of the side-effects common with chemotherapy. The extent of hematologic recovery during a course of cheotherapy often dictates the feasibility of delivering tumor control doses and the possibility of concurrent or adjuvant chemotherapy. The usefulness of this proposal to assess quantative changes in hematological recovery by lithium may hold promise for future clinical applications since many results originally accumulated through the use of animal models has provided information applicable to man. The understanding of the mechanisms whereby lithium may augment hematopoietic recovery or lessen hematopoietic damage may lead to improvements in chemotherapy protocols.
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