The effect of dideoxycytidine on lymphocyte subpopulations in nonhuman primates.
In the present study, 2',3'-dideoxycytidine (ddC), which has antiretroviral activity, was given chronically to uninfected nonhuman primates to determine whether it produces adverse immunological or hematological effects. Nine healthy adult male rhesus monkeys were divided into three groups and given the following doses of ddC in a gelatin vehicle: group A, 0.06, 6.0, 3.0, and 1.5 mg/kg; group B, 0.6 mg/kg; group C, 0 mg/kg. Blood samples were collected for hematologic analysis and flow cytometric analyses of lymphocyte subpopulations. Chronic ddC exposure did not cause significant changes in the number of red blood cells, monocytes, or reticulocytes. The number of white blood cells and neutrophils increased and these changes were observed only in group A animals at the 1.5 mg/kg dose. The most significant alterations observed were decreases in the number of T helper cells (CD4) and B cells (CD20). CD4+ and CD20+ lymphocytes exhibited dose-related shifts that were reversible over time and after drug withdrawal. The results indicate that ddC has few hematologic effects but it does have profound but transient effects on the number of cells in lymphocyte subpopulations in normal primates.
Taylor
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LD
Division of Genetic Toxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079.
Binienda
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Schmued
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Slikker
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D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001773:Blood Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D016047:Zalcitabine / Q000633:toxicity*
D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D016047:Zalcitabine