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N-methyl-N-nitrosourea alters thymocyte subset distribution and targets immature CD4-8+ cells for lymphoma development.

Abstract
The majority of N-methyl-N-nitrosourea (MNU)-induced lymphomas in AKR/J mice express a CD4-8+ phenotype. The CD4-8+ subset in normal thymus contains functionally mature medullary cells and immature cycling cells. This study demonstrates that MNU-induced lymphomas correspond to the immature CD4-8+ subset. In addition, specific changes in the distribution of thymocyte subsets defined by CD4 and CD8 expression were observed after MNU treatment. Cortical thinning and selective depletion of immature CD4-8+ and CD4+8+ subsets occur immediately after treatment. In contrast, immature CD4-8- progenitors and mature medullary CD4+8- and CD4-8+ subsets are relatively resistant to cytotoxicity. Normal thymic architecture and subset distribution are restored within 2 weeks after which selective expansion of the immature CD4-8+ subset occurs. The data suggest that MNU induces neoplastic conversion in progenitor cells corresponding to the CD4-8- or immature CD4-8+ stages of thymocyte maturation.
AuthorsS L Stettner, S A Rummel, C J Conti, E R Richie
JournalCancer research (Cancer Res) Vol. 51 Issue 2 Pg. 737-40 (Jan 15 1991) ISSN: 0008-5472 [Print] United States
PMID1898715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Methylnitrosourea
Topics
  • Animals
  • Antigens, Differentiation, T-Lymphocyte (analysis)
  • CD4 Antigens (analysis)
  • CD8 Antigens
  • Lymphoma (chemically induced, immunology)
  • Methylnitrosourea (toxicity)
  • Mice
  • Mice, Inbred AKR
  • T-Lymphocyte Subsets (drug effects, immunology)
  • Thymus Gland (drug effects, immunology, pathology)
  • Thymus Neoplasms (chemically induced, immunology, pathology)

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