title: 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.
authors.affiliation: University of Texas, M. D. Anderson Cancer Center, Smithville 78957.
authors.forename: S L
authors.initials: SL
authors.lastname: Stettner
authors.forename: S A
authors.initials: SA
authors.lastname: Rummel
authors.forename: C J
authors.initials: CJ
authors.lastname: Conti
authors.forename: E R
authors.initials: ER
authors.lastname: Richie
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens; D008223:Lymphoma / Q000139:chemically induced* / Q000276:immunology; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008806:Mice, Inbred AKR; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D013953:Thymus Neoplasms / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D008770:Methylnitrosourea