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

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.