Hemopoietic progenitor cells ave sensitive targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J mice

Treatment of adult C57BL/6J mite 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 dth 30 mu g/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 mu g/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.