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) el icits altered bone marrow hemopoietic cellular potentials and markedly redu ced T-lymphoid-reconstituting activity. The latter has been hypothesized to play a role in TCDD-induced thymic atrophy. To investigate cellular target s responsible for reduced prothymocyte capacity, bone marrow cells from TCD D-treated C57BL/6J mice were assessed for hemopoietic alterations within th e lineage-negative (lin(-)) compartment by the examination of Sca-1 and c-K it levels. Lin(-) hemopoietic cells from C57BL/6J mice, treated dth 30 mu g /kg of TCDD, were assessed for phenotypic alterations following 24 h throug h 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(+) cell s, relative to control, over 24 h through 31 days following treatment, as w ell 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 b asis and were also dependent upon TCDD dose. These data suggest that prolif eration and/or differentiation processes of hemopoietic stem cells are affe cted by TCDD and that these effects contribute to a reduced capacity of bon e marrow to generate pro-T lymphocytes.