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Toxicological Sciences 54, 374-383 (2000)
Copyright © 2000 by the Society of Toxicology

Hemopoietic Progenitor Cells Are Sensitive Targets of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in C57BL/6J Mice

Francis G. Murante1 and Thomas A. Gasiewicz

Department of Environmental Medicine, University of Rochester, Rochester, New York 14642

Treatment of adult C57BL/6J mice with tetrachlorodibenzo-p-dioxin (TCDD) elicits altered bone marrow hemopoietic cellular potentials and markedly reduced T-lymphoid-reconstituting activity. The latter has been hypothesized to play a role in TCDD-induced thymic atrophy. To investigate cellular targets responsible for reduced prothymocyte capacity, bone marrow cells from TCDD-treated C57BL/6J mice were assessed for hemopoietic alterations within the lineage-negative (lin) compartment by the examination of Sca-1 and c-Kit levels. Lin hemopoietic cells from C57BL/6J mice, treated with 30 µg/kg of TCDD, were assessed for phenotypic alterations following 24 h through 31 days. The responses of lin cells to TCDD doses ranging from 0.3 to 30 µg/kg were also assessed at 2 days following TCDD treatment. The data reveal increases in the number of bone marrow lin Sca-1+ c-Kit+ cells, relative to control, over 24 h through 31 days following treatment, as well as dose-dependent increases in this population when examined at 2 days. Increases in lin Sca-1+ c-Kit cells occurred on a more transient basis and were also dependent upon TCDD dose. These data suggest that proliferation and/or differentiation processes of hemopoietic stem cells are affected by TCDD and that these effects contribute to a reduced capacity of bone marrow to generate pro-T lymphocytes.

Key Words: tetrachlorodibenzo-p-dioxin; TCDD; hemopoiesis; Sca-1; c-Kit; hemopoietic stem cells; flow cytometry.


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