Document 0823
 DOCN  M9590823
 TI    2'3'-Dideoxycytidine-induced thymic lymphoma correlates with
       species-specific suppression of a subpopulation of primitive
       hematopoietic progenitor cells in mouse but not rat or human bone
       marrow.
 DT    9509
 AU    Irons RD; Le AT; Som DB; Stillman WS; School of Pharmacy, University of
       Colorado Health Sciences; Center, Denver 80262, USA.
 SO    J Clin Invest. 1995 Jun;95(6):2777-82. Unique Identifier : AIDSLINE
       MED/95286843
 AB    The nucleoside analogue, 2',3'-dideoxycytidine (ddC), is a potent
       inhibitor of HIV replication, and AIDS patients receiving ddC experience
       clinical improvement without significant hematologic toxicity. Repeated
       ddC administration (1,000 mg/kg per day) for 13 wk produces an increased
       incidence of thymic lymphoma in B6C3F1 mice. Previous studies reveal a
       common link between chemically induced and genetically associated models
       of mouse thymic lymphoma that involves a defect in a subpopulation of
       primitive hematopoietic progenitor cells. This defect is characterized
       by suppression of a subpopulation of IL-3-responsive cells and ablation
       of stem cell factor synergy with GM-CSF. The present study was
       undertaken to ascertain whether ddC produces the same pattern of bone
       marrow toxicity in mice, and whether this effect is observed in rat and
       human bone marrow. ddC exposure in vivo and in vitro produced a select
       suppression of murine CFU identical to that previously described for
       other models of mouse thymic lymphoma. In contrast, this selective CFU
       suppression was not observed in rat and human bone marrow or in CD34+
       cells. These studies suggest that the mouse may not be a good predictive
       model for ddC hematotoxicity in humans and that susceptibility to the
       development of thymic lymphoma may be unique to the mouse.
 DE    Adult  Animal  Bone Marrow/CYTOLOGY/*DRUG EFFECTS  Colony-Forming Units
       Assay  Comparative Study  Granulocyte-Macrophage Colony-Stimulating
       Factor/PHARMACOLOGY  Hematopoiesis/*DRUG EFFECTS  Hematopoietic Cell
       Growth Factors/PHARMACOLOGY  Hematopoietic Stem Cells/*DRUG EFFECTS
       Human  Interleukin-3/PHARMACOLOGY  Lymphoma, T-Cell/*CHEMICALLY INDUCED
       Male  Mice  Mice, Inbred C57BL  Rats  Recombinant Proteins  Species
       Specificity  Support, Non-U.S. Gov't  Thymus Neoplasms/*CHEMICALLY
       INDUCED  Zalcitabine/*PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).