Title: The thymus does not mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin-elicited alterations in bone marrow lymphocyte stem cells.
Authors: Frazier Jr, D E; Silverstone, A E; Soults, J A; Gasiewicz, T A
Published In Toxicol Appl Pharmacol, (1994 Feb)
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 micrograms/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.
PubMed ID: 8122269
MeSH Terms: Animals; Bone Marrow/drug effects*; Bone Marrow/ultrastructure; Cells, Cultured; DNA Nucleotidyltransferases/biosynthesis; Female; Genes, RAG-1/drug effects; Liver/drug effects; Liver/metabolism; Lymphocytes/drug effects*; Lymphocytes/metabolism; Lymphocytes/ultrastructure; Mice; Mice, Inbred BALB C; Mice, Nude; Organ Size/drug effects; Polychlorinated Dibenzodioxins/pharmacology*; Receptors, Aryl Hydrocarbon/drug effects; Stem Cells/drug effects*; Stem Cells/ultrastructure; Thymectomy; Thymus Gland/drug effects; Thymus Gland/metabolism; Thymus Gland/physiology*