Molecular and Cellular Radiobiology Project Title: 17. Effects of Radiation and Chemicals on Control of Hemopoiesis RX-03-02-(b) Expected Results in FY 1974: (Cont'd,) time the chambers will be removed; the animal given fatal whole-body irradiation and its HSC's grown in culture harvested from the diffusion chambers and then injected into the goat to test protective ability. Human blood leukocytes will be fractionated into "“pure'' cell types to see whether the HSC present in blood will grow and differentiate in the absence of mature cell types. With this model system one should be able to evaluate the influence of cell-to-cell interaction in addition to the long-range and long-duration feedback loops from the periphery to the stem cell. In analyzing the preceding, DNA content, and cytology will be observed, sequence of tritiated thymidine labeling, Further studies on granulopoiesis will be performed before and after the induction of inflammation at various time intervals in order to dissect the sequence of events at the myelocyte level and the HSC level that determine the increased production of granulocytes, Studies on the growth of leukemic cells and cells from other blood dyscrasias will continue as clinical material is available. 18. Expected Results in FY 1975: Fe-55 suicide will continue--the actual use of this new technique depending upon the results obtained in FY 1974, The studies on Dy, of human stem cells will probably be completed, Studies on the diffusion chamber factor and determination of whether it is identical to the CSF and/or the leukocytosis-inducing factor (LIF) will continue if the problems are not resolved in FY 1974. The autologous culture cf bone marrow cells in animals will continue in an endeavor to determine the importance of cell-to-cell interaction by implanting diffusion chambers into diverse organs, Attempts will be made to develop long-term monocyte cultures as a source of CSF, LIF, and diffusion chamber stimulatory factor, EP production in human glomerular cultures should be sufficient for the production of adequate amounts of antisera for radioimmuno-assay in patients, It is hoped to produce radioactive EP with sufficient specific activity suitable for autoradiography. When satisfactory radioactive EP is avpilable it will be utilized in vitro, in erythropoietic cultures, and in m to study metaphase of erythropoietic cells. The genetic locus of om giv may be identified in this manner. Consideration will also be a pilot plant for production of human EP for possible clinical application. Studies on the role of inflammation and the mechanism by which it increases cell proliferation may terminate, Studies on cell proliferation in leukemia will continue. The studies on platelet transfusions and control of thrombopoiesis in collaboration with Valeri will probably be reactivated. (See Continuation Sheet) 1119292 RX- 232