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

Abstract

Treatment of adult C57BL6J 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 microg/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 microg/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.

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

“…Likewise, the Tg mice we developed in the present study enable a new approach to explore the effect of AhR activation in T cells in the immune suppression. Lymphocyte progenitor cells have been reported to be affected by TCDD, and its effect was suggested to contribute to a loss of thymocytes (48,49). Although the expression of CA-AhR in the lymphocyte progenitor cells was much fainter than that in the thymocytes and T cells (Figs.…”

Aryl Hydrocarbon Receptor-Null Allele Mice Have Hematopoietic Stem/Progenitor Cells with Abnormal Characteristics and Functions

“…With this in mind, and because TCDD-induced AhR dysregulation alters the number of murine LSK BM cells [17,20], we evaluated the number of hematopoietic precursors in the BM of KO and their littermate HZ mice using a FIG. 2.…”

“…Pre-or postnatal TCDD exposure results in a significant reduction in lymphoid-specific TdT and RAG-1 mRNA in BM, and thymic seeding by BM cells from TCDDtreated animals is substantially decreased [16]. However, TCDD treatment produces a significant increase in the number of hematopoietic stem cell (HSC)-enriched Lin À Sca-1 þ c-Kit þ (LSK) cells [17,18]. The use of radiation chimeras demonstrated that the presence of the AhR in hematopoietic cells, but not supporting stroma, was responsible for these effects [19].…”

Persistent hematologic and immunologic disturbances in 8-year-old Dutch children associated with perinatal dioxin exposure.

“…Murante and Gasiewicz (2000) reported effects of TCDD exposure on marrow progenitor cells in mice. Their data indicate that proliferation and/or differentiation processes of hemopoietic stem cells are influenced by TCDD administered 5-6 weeks postpartum.…”