The thymus does not mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin-elicited alterations in bone marrow lymphocyte stem cells.
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.
Frazier
D E
DE
Department of Environmental Medicine, University of Rochester School of Medicine, New York 14642.
Silverstone
A E
AE
Soults
J A
JA
Gasiewicz
T A
TA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000648:ultrastructure; D002478:Cells, Cultured; D004254:DNA Nucleotidyltransferases / Q000096:biosynthesis; D005260:Female; D016654:Genes, RAG-1 / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000648:ultrastructure; D013934:Thymectomy; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D004254:DNA Nucleotidyltransferases