The Thymus Does Not Mediate 2,3,7,8-Tetrachlorodibenzo- p-dioxin-Elicited Alterations in Bone-Marrow Lymphocyte Stem Cells

Abstract

Our previous studies have shown that bone marrow lymphocyte stem cells are affected following perinatal or adult exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). These alterations may, in part, be responsible for thymic atrophy that is also observed following TCDD exposure. However, other investigators have suggested that the thymus or thymic-derived lymphocytes can affect bone marrow stem cell development. The purpose of these studies was to determine whether the TCDD-elicited effects that we have observed on lymphocyte stem cells in bone marrow were secondary to the actions of this chemical on the thymus. A single intraperitoneal dose of TCDD (30 μg/kg) to sham-operated or neonatally thymectomized female BALB/c mice reduced the levels of mRNA in the bone marrow for the lymphocyte stem cell-specific enzymes terminal deoxynucleotidyl transferase (TdT) and recombinase activating gene (RAG-1). TdT biosynthesis was also reduced by TCDD treatment. Thus, neonatal thymectomy had no effect on the TCDD-elicited reduction of TdT or RAG-1 mRNAs or TdT biosynthesis. Genetically athymic (nu/nu) mice were used to further determine if the actions of TCDD on the thymus or long-lived T-cells altered lymphocyte stem cell development. As observed in BALB/c mice, TCDD treatment decreased the expression of TdT and RAG-1 mRNAs in bone marrow from athymic nu/nu and intact nu/+ littermates. We conclude that TCDD-elicited alterations in bone marrow lymphocyte stem cells are not secondary to any actions, direct or indirect, that TCDD has on the thymus or thymic-derived T-cells.