THE OBJECTIVE OF THE PROJECT IS TO ESTABLISH HUMAN HEMATO- POIETIC PROGENITOR GROWTH FACTOR-DEPENDENT CELL LINES IN CULTURE.

THE OBJECTIVE OF THE PROJECT IS TO ESTABLISH HUMAN HEMATO- POIETIC PROGENITOR GROWTH FACTOR-DEPENDENT CELL LINES IN CULTURE. TO ACCOMPLISH THIS, RESEARCHERS WILL FIRST DESIGN AND CONSTRUCT RETROVIRAL VECTORS THAT CAN INFECT AND EXPRESSCLONED GENES IN APPROPRIATE CELL TYPES. THESE WOULD CARRY BOTH A SELECTABLE MARKER GENE AND AN ONCOGENE. SECOND, RESEARCHERS WILL ESTABLISH MURINE CELL LINES PRODUCING THE ENGINEERED RETROVIRUSES AND DEVELOP ASSAYS TO ENABLE THEM TOOBTAIN REPRODUCIBLY HIGH VIRUS TITRES AND MONITOR EXPRESSIONOF THE ONCOGENE(S) USED. RESEARCHERS WILL THEN INFECT ENRICHED POPULATIONS OF HUMAN HEMATOPOIETIC PROGENITOR CELLSAND CULTURE THESE IN THE PRESENCE (OR ABSENCE) OF DEFINED GROWTH/DIFFERENTIATION FACTORS OR CONDITIONED MEDIA FROM HUMAN T-CELL LINES KNOWN TO PRODUCE LYMPHOKINES. FINALLY, RESEARCHERS WILL ISOLATE INDIVIDUAL CELL LINES FROM THE INFECTED CELLS AND SCREEN THESE FOR GROWTH FACTOR DEPENDENCE/INDEPENDENCE. SUCH CELL LINES WOULD BE INVALU- ABLE IN THE ISOLATION, CHARACTERIZATION, AND FUNCTIONAL OPTIMIZATION OF THESE, AND OTHER, BIOLOGICAL RESPONSE MODIFIERS AND THEIR SPECIFIC CELL SURFACE RECEPTORS. IN ADDITION, THEY WOULD BE EXTREMELY USEFUL AS RESEARCH TOOLS TO STUDY HEMATOPOIESIS AND COULD BECOME VALUABLE IN DRUG SCREENING PROGRAMS TO ASSESS AGENTS AIMED AT PROLIFERATIVE DISORDERS OF THE HEMATOPOIETIC SYSTEM AND TO MEASURE POTENTIAL SIDE EFFECTS OF OTHER CHEMOTHERAPEUTIC AGENTS.