Molecular and Cellular Radiobiology Project Title: 14, Scope: Effects of Radiation and Chemicals on Control of Hemopoiesis RX-03-02- (b) (Cont'd.) Studies in man are aimed at é@lucidation of the defect population of cells compared to normal cell proliferation. in the leukemic Leukemia is studied by a combination of techniques: measurement of cell kinetics following administration of tritiated thymidine; serial sampling of the bone marrow and peripheral blood; culture of leukemic cells in diffusion chambers implanted into the mouse complemented by in vitro culture; and measurement of DNA content (when facilities are acquired). The enzyme profile and the karyotopes of chronic granulocytic Leukemia cells are studied before and after culture of cells in diffusion chambers. Radiobiological studies are concerned with determination of the De of the human HSC required for radiation therapy and space flight and the relative biological effectiveness the CFUs,. 15, (RBE) of various neutron energie® on. ‘ Relationship to Other Projects: The studies on lymphopoiesis reported in RX-01-03-(d) are a closely related research program. Elsewhere, related studies include those of Lewis, Trobaugh, Fried and Knospe, St. Luke's Hospital, University of Illinois, on factors in the ° bone marrow and spleen which support hematopoiesis, and the hemopoietic ’ inductive micro-environment in the spleen and bone marrow, Till and McCulloch, Department of Biophysics, University of Toronto, the initiators of the splenic colony work, are concerned with short- and long-term feedback loops regulating growth, differentiation of the stem cell, the effects of drugs on the stem cell and the relationship of the stem cell to leukemia. Stohlman and Quesenberry, St. apply splenic colony formation, Elizabeth's Hospital, Brighton, Massachusetts erythropoietin administration, in vitro bone marrow culture, and more recently the diffusion chamber technique learned at BNL, to study growth kinetics and factors related to erythropoiesis and granulopoiesis. Benestad, Breivik and Boyum, Oslo, Norway, the developers of the diffusion chamber technique for study of hematopotesis, continue its application to ascertain the nature of the factors which influence stem cell proliferation and differentiation. ies inson, University of Colorado Medical Center, uses the in vitro of murine and human blood bone marrow cells in patients with various pscrasias and in studying the regulatory factors concerned with granulocytopoiesis., Rothstein, Athens, and Cartwright, University of Utah, apply the in vitro culture of bone marrow and blood cells along with a modification of themillipore diffusion chambers to study stem cell proliferation, differentiation, and factors regulating granulocytopoiesis, (See Continuation Sheet) 1119288 RX- 228