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National Institute of Environmental Health Sciences

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Publication Detail

Title: Interleukin-3 increases the incidence of 5-azacytidine-induced thymic lymphomas in pBOR-Il-3 mice.

Authors: Saavedra, H I; Wang, T H; Hoyt, P R; Popp, D; Yang, W K; Stambrook, P J

Published In Cell Immunol, (1996 Oct 10)

Abstract: Interleukin-3 (Il-3) is a glycoprotein produced by a CD4+CD8- subpopulation of T-lymphocytes. Il-3 has been associated with the proliferation of bone marrow stem cells and their differentiation to granulocytes, macrophages, basophil/mast cells, megakaryocytes, erythroid cells, and neutrophils. The pBOR-Il-3 transgenic mice were developed by pronuclear microinjection to study how chemical insults modulate transcription of the Il-3 gene driven by a long-terminal repeat (LTR) of an endogenous retrovirus and to determine the biological consequences of interleukin-3 expression. We injected 5-azacytidine, a demethylating agent, to increase the LTR-driven expression of Il-3. Upon 5-azacytidine treatment, both the pBOR-Il-3 and the FVB/N nontransgenic controls developed thymic lymphomas. The pBOR-Il-3 mice developed thymic lymphomas at a higher frequency than the FVB/N mice. The thymic lymphoma cells were of a T-cell origin, as determined by T-cell receptor gene rearrangement analysis, and, in most cases, were of monoclonal origin. According to flow cytometric analysis of CD3, CD4, and CD8 cell surface markers, the thymic lymphoma cells did not lose their ability to differentiate, but the differentiation process was aberrant. Flow cytometric analyses also revealed that in pBOR-Il-3 mice the thymic lymphomas are mostly of a CD8+CD4- origin, whereas in the FVB/N group, the predominant type of thymic lymphoma is of a CD4+CD8- origin.

PubMed ID: 8871607 Exiting the NIEHS site

MeSH Terms: Animals; Azacitidine/pharmacology; CD3 Complex/immunology; CD4 Antigens/immunology; CD8 Antigens/immunology; Carcinogens/pharmacology; Disease Models, Animal; Female; Gene Rearrangement, T-Lymphocyte; Incidence; Interleukin-3/immunology*; Interleukin-3/pharmacology; Male; Mice; Mice, Transgenic; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology*; Thymus Neoplasms/genetics; Thymus Neoplasms/immunology*

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