title: TCDD treatment eliminates the long-term reconstitution activity of hematopoietic stem cells.
abstract: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disrupting chemical (EDC), can cause carcinogenesis, immunosuppression, and teratogenesis, through a ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Despite remarkable recent advances in stem cell biology, the influence of TCDD on hematopoietic stem cells (HSCs), which possess the ability to reconstitute long-term multilineage hematopoiesis, has not been well investigated. In this study we examined the influence of TCDD on HSCs enriched for CD34(-), c-kit(+), Sca-1(+), lineage negative (CD34-KSL) cells. The number of the CD34-KSL cells was found to be increased about four-fold upon a single oral administration of TCDD (40 micro g/kg body weight). Surprisingly, we found that these TCDD-treated cells almost lost long-term reconstitution activity. This defect was not present in AhR(-/-) mice. These findings suggest that modulation of AhR/ARNT system activity may have an effect on HSC function or survival.
authors.affiliation: Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Ruriko
authors.initials: R
authors.lastname: Sakai
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Kajiume
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inoue
authors.forename: Rieko
authors.initials: R
authors.lastname: Kanno
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Masamoto
authors.initials: M
authors.lastname: Kanno
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004785:Environmental Pollutants / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon