TCDD treatment eliminates the long-term reconstitution activity of hematopoietic stem cells.
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.
Sakai
Ruriko
R
Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
Kajiume
Teruyuki
T
Inoue
Hiroko
H
Kanno
Rieko
R
Miyazaki
Masaki
M
Ninomiya
Yuichi
Y
Kanno
Masamoto
M
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
D018952:Antigens, CD34; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon