The effects of cocaine injections on mouse thymocyte population.
C57 BL mice were injected daily with either saline or varied doses of cocaine (5-50 mg/kg), and thymocyte subpopulations were analyzed 4 hr after the fifth injection. Mice injected with either 25 or 50 mg/kg of cocaine showed a decrease in the percentage of CD4+8+ cells and increase of CD4-8-, CD4+, and CD8+ cells. The absolute numbers of each subpopulation, calculated by multiplying the percentage of each subpopulation with the total cell number, revealed an extensive decline in CD4+8+, a decrease in CD8+, an increase in CD4-8-, and no change in the CD4+ subpopulation. Flow cytometric analysis of thymocytes and electrophoresis of the thymocyte DNA revealed a dosage-dependent increase in cells undergoing programed cell death with apoptosis. Culturing of thymocytes from control or drug-treated mice demonstrated an inverse relationship between cell viability and cocaine concentrations, suggesting that in vivo cocaine, or its biological products, may damage thymocytes. Incubation of normal cells with cocaine showed a dose-dependent decrease of viability with identical patterns of the alteration of cell subpopulations observed in vivo. A dose-dependent increase of apoptosis was also observed. In summary, we demonstrate a selective in vivo cocaine-induced alteration of the thymocyte subpopulations and identified programed cell death with apoptosis as the likely mechanism mediating this thymic atrophy. The comparable findings observed in vivo and in vitro support the concept that cocaine may directly affect some features of thymocyte biology, and suggest the usefulness of the in vitro system in studying cocaine effects on thymocyte biology.
Wu
Y B
YB
VA West Side Medical Center, Chicago, Illinois 60612, USA.
Shen
M L
ML
Gu
G G
GG
Anderson
K M
KM
Ou
D W
DW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003042:Cocaine / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D007267:Injections; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects
D004247:DNA; D003042:Cocaine