Document 2864
 DOCN  M94A2864
 TI    Toxicity and carcinogenicity of dideoxycytidine in mice.
 DT    9412
 AU    Rao G; Sanders V; Elwell M; Giles H; Heath J; Lindamood C 3rd; NIEHS,
       NIH, Res. Tri. Park, NC 27709.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):207 (abstract no. PB0259). Unique
       Identifier : AIDSLINE ICA10/94369711
 AB    OBJECTIVE: The 2',3'-dideoxycytidine (ddC) is an approved nucleoside for
       treatment of HIV positive patients. The purpose of the project is to
       evaluate the toxic and carcinogenic potential of ddC by short-term
       studies in two different mouse models. METHODS: The hybrid B6C3F1 mouse
       with ecotropic proviral sequences that can be activated and NIH-Swiss
       mouse with proviral sequences that cannot be expressed were treated with
       ddC by gavage at 500 and 1000 mg/kg for up to 6 months and evaluated for
       hematotoxicity and pathologic changes. RESULTS: In NIH-Swiss mice the
       ddC caused thymic lymphoma with involvement of other organs and ovarian
       tumors by 3 months at 1000 mg/kg, and thymic lymphoma with involvement
       of other organs by 4 months at 500 mg/kg. The ddC also caused thymic
       lymphoma in B6C3F1 mice by 3 months at 1000 mg/kg and by 6 months at 500
       mg/kg. In addition, anemia, bone marrow toxicity, and thymic atrophy
       were observed in both strain/stock mice. DISCUSSION AND CONCLUSION:
       Studies to determine cell markers of ddC-induced lymphoma lymphocytes
       and genetic changes in ddC-induced tumors are in progress. These studies
       may help in understanding the mechanism of carcinogenesis by ddC. Based
       on the mouse models, ddC has the potential to cause lymphoma and other
       neoplasms. This risk should be considered in long-term treatment of HIV
       positive patients with ddC, especially children and adolescent patients.
 DE    Anemia/*CHEMICALLY INDUCED  Animal  Bone Marrow Diseases/*CHEMICALLY
       INDUCED  Carcinogenicity Tests  Comparative Study  Female
       Lymphoma/*CHEMICALLY INDUCED  Mice  Ovarian Neoplasms/*CHEMICALLY
       INDUCED  Species Specificity  Thymus Neoplasms/*CHEMICALLY INDUCED
       Tumor Viruses, Murine/DRUG EFFECTS  Virus Activation/DRUG EFFECTS
       Zalcitabine/*TOXICITY  MEETING ABSTRACT

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