Project Title: 15. Combating Detrimental Effects of Radiation The Role of Stem Cell and Therapy of the Hemorrhagic Phase in Radiation Injury Relationship to Other Projects: (Cont'd.) RX-01-02 Hopkins Medical Center, are interested in the effects of drugs on stem cell growth, with essentially no work related to radiation effects, The studies involving cyclophosphamide effects are closely related to studies here: Sensenbrenner collaborates with BNL on the diffusion chamber technique. H. Ragan, Battelle Northwest, who learned the diffusion chamber technique at BNL, is interested in the effects of internal emitters on the hematopoietic system. Stohlman's group at St. Elizabeth's Hospital, Brighton, Massachusetts, is interested in all aspects of normal and abnormal hematopoiesis. Benestad of the Norwegian Defense Research Establishment was a key figure in the development of the implanted diffusion chamber and the application of his method in collaboration with his colleague, A. Boyum, a former Research Collaborator in Residence at BNL. 16, Technical Progress in FY 1973: Attempts to produce large numbers of HSC in diffusion chamber cultures have to date been unsuccessful, potential clinical application, Attempts will continue in view of the During this year the diffusion chamber culture technique has been / applied to the study of bone marrow. from patients with various blood dyscrasias, Nine patients were studied (chronic myeloid leukemia 4, acute myelomonocytic leukemia 3, myelofibrosis with myeloid metaplasia 2, polycythemia vera 1), These observations were compared with the growth patterns of 3 normal bone marrow samples, In normal bone marrow an orderly maturation of cells took place similar to that seen in vivo. Autoradiographic studies on marrow from the patients with acute myelocytic and chronic myelocytic leukemia suggested a faster maturation rate than that previously reported. The rate of maturation in the diffusion — chamber may be somewhat slower in myelofibrosis and chronic myeloid leukemia (CML) as compared with che normal individual. When bone marrow from patients with Ph, + CML and leukocyte alkaline phosphatase . (LAP) negative cells is grown in diffusion chambers the Ph) + mitoses persist but a progeny of intensely positive LAP cells emerges. This proves that LAP negativity is-not due to loss of LAP genomes when deletion of autosome 23 produced _ the e + chromosome. The LAP negativity is due to repression of the genomes carryahi the code for LAP in CML. Their derepression by factors supplied by the néligine environment results in LAP + cells. The RBE of the CFU has been studied using the spleen colony technique in mice exposed to various energy of neutrons. The Do values obtained were as follows: 250 KVp x rays - 80.14 rads, reactor fission neutrons40.78 rads, accelerator neutrons - 0.4 MeV - 28.14 rads; 0.66 MeV neutrons 34.50 rads; 1.0 MeV neutrons - 28.12 rads; 1.5 MeV neutrons - 28.8 rads; 1.8 MeV neutrons - 29,62 rads. (See Continuation Sheet) 1149190 RX-30