The overall goals of this project are: (1) to continue our longstanding studies of the biological aspects of murine lymphomagenesis induced by radiation and related viruses. Specifically, we wish to define the cell population(s) in the bone marrow of irradiated mice which contains the novel transmissible lymphomagen, as a first step in its identification, and also as an important step in reconciling normal and neoplastic hematolymphoid cell differentiation lineages. Similar techniques of cell separation based on immunomagnetic bead separation technology, followed by flow cytometry will be used to identify normal bone marrow cells which prevent radiation lymphomagenesis; and also target cells for neoplastic transformation. The role of stromal cells in the progression of preleukemic cells will be analyzed. The studies in the murine model will be extended to a direct examination of the effects of radiation and of human lymphotropic viruses (HTLV-I and HTLV-II) on human organ systems in vivo, by making use of our recently described hematochimeric SCID-hu mice. The parameters which we have worked out in murine radiation lymphomagenesis will be tested in the SCID-hu system. With respect to the human retroviruses, evidence of infection will be sought following their inoculation in SCID-hu mice and, if detected, the course of disease pathogenesis will be evaluated. Because of its potential value to the study of human disease, major emphasis will be placed on this aspect of the project.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA003352-33A1
Application #
3163136
Study Section
Pathology B Study Section (PTHB)
Project Start
1979-04-01
Project End
1992-04-30
Budget Start
1989-07-01
Budget End
1990-04-30
Support Year
33
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Sen-Majumdar, A; Guidos, C; Kina, T et al. (1994) Characterization of preneoplastic thymocytes and of their neoplastic progression in irradiated C57BL/Ka mice. J Immunol 153:1581-92
Sen-Majumdar, A; Weissman, I L; Hansteen, G et al. (1994) Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire of T-cell receptor V beta gene products. J Virol 68:1165-72
Small, M; Majumdar, A S; Lieberman, M et al. (1994) Isolation of CD3-, CD4-, CD8-, IL-2R+ thymocyte precursors by panning. J Immunol Methods 167:103-7
Waller, E K; Ziemianska, M; Bangs, C D et al. (1993) Characterization of posttransplant lymphomas that express T-cell-associated markers: immunophenotypes, molecular genetics, cytogenetics, and heterotransplantation in severe combined immunodeficient mice. Blood 82:247-61
Sen-Majumdar, A; Lieberman, M; Alpert, S et al. (1992) Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture. J Exp Med 176:543-51
Waller, E K; Sen-Majumdar, A; Kamel, O W et al. (1992) Human T-cell development in SCID-hu mice: staphylococcal enterotoxins induce specific clonal deletions, proliferation, and anergy. Blood 80:3144-56
Lieberman, M; Hansteen, G A; Waller, E K et al. (1992) Unexpected effects of the severe combined immunodeficiency mutation on murine lymphomagenesis. J Exp Med 176:399-405
Waller, E K; Kamel, O W; Cleary, M L et al. (1991) Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment. Blood 78:2650-65
Majumdar, A S; Guidos, C; Kaneshima, H et al. (1990) An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets. J Immunol 144:111-21
McCune, J M; Kaneshima, H; Lieberman, M et al. (1989) The scid-hu mouse: current status and potential applications. Curr Top Microbiol Immunol 152:183-93

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