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M94A2864.TXT
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1994-10-25
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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).