ToxSci Advance Access originally published online on February 18, 2003
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Toxicological Sciences 72, 84-91 (2003)
Copyright © 2003 by the Society of Toxicology
IMMUNOTOXICOLOGY |
TCDD Treatment Eliminates the Long-Term Reconstitution Activity of Hematopoietic Stem Cells
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* Department of Immunology, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan;
Japanese Society for the Promotion of Science Research Fellowship for Young Scientists; and
CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
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*plus;, 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 µg/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.
Key Words: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; hematopoietic stem cells (HSCs); CD34-KSL (CD34-, c-kit+, Sca-1+, lineage negative) cells; long-term reconstitution activity; aryl hydrocarbon receptor; AhR.
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